$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2
Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is nega...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Vestey, SB [verfasserIn] Sen, C [verfasserIn] Calder, CJ [verfasserIn] Perks, CM [verfasserIn] Pignatelli, M [verfasserIn] Winters, ZE [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2004 |
|---|
| Schlagwörter: |
|---|
| Anmerkung: |
© Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
|---|
| Übergeordnetes Werk: |
Enthalten in: Breast cancer research - BioMed Central, 1999, 6(2004), 5 vom: 29. Juli |
|---|---|
| Übergeordnetes Werk: |
volume:6 ; year:2004 ; number:5 ; day:29 ; month:07 |
| Links: |
|---|
| DOI / URN: |
10.1186/bcr912 |
|---|
| Katalog-ID: |
SPR029921619 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR029921619 | ||
| 003 | DE-627 | ||
| 005 | 20240426065201.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201007s2004 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/bcr912 |2 doi | |
| 035 | |a (DE-627)SPR029921619 | ||
| 035 | |a (SPR)bcr912-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.00 |2 bkl | ||
| 100 | 1 | |a Vestey, SB |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 |
| 264 | 1 | |c 2004 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. | ||
| 520 | |a Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. | ||
| 650 | 4 | |a ARF protein |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a ductal carcinoma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hdm2 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a HER-2 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a immunohistochemistry |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Sen, C |e verfasserin |4 aut | |
| 700 | 1 | |a Calder, CJ |e verfasserin |4 aut | |
| 700 | 1 | |a Perks, CM |e verfasserin |4 aut | |
| 700 | 1 | |a Pignatelli, M |e verfasserin |4 aut | |
| 700 | 1 | |a Winters, ZE |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Breast cancer research |d BioMed Central, 1999 |g 6(2004), 5 vom: 29. Juli |w (DE-627)326645950 |w (DE-600)2041618-0 |x 1465-542X |7 nnns |
| 773 | 1 | 8 | |g volume:6 |g year:2004 |g number:5 |g day:29 |g month:07 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/bcr912 |m X:SPRINGER |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 912 | |a SYSFLAG_0 | ||
| 912 | |a GBV_SPRINGER | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a GBV_ILN_11 | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 936 | b | k | |a 44.00 |q VZ |
| 951 | |a AR | ||
| 952 | |d 6 |j 2004 |e 5 |b 29 |c 07 | ||
| author_variant |
s v sv c s cs c c cc c p cp m p mp z w zw |
|---|---|
| matchkey_str |
article:1465542X:2004----::1afxrsinnnaieratacradutlacnmistrl |
| hierarchy_sort_str |
2004 |
| bklnumber |
44.00 |
| publishDate |
2004 |
| allfields |
10.1186/bcr912 doi (DE-627)SPR029921619 (SPR)bcr912-e DE-627 ger DE-627 rakwb eng 610 VZ 44.00 bkl Vestey, SB verfasserin aut $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. ARF protein (dpeaa)DE-He213 ductal carcinoma (dpeaa)DE-He213 Hdm2 (dpeaa)DE-He213 HER-2 (dpeaa)DE-He213 immunohistochemistry (dpeaa)DE-He213 Sen, C verfasserin aut Calder, CJ verfasserin aut Perks, CM verfasserin aut Pignatelli, M verfasserin aut Winters, ZE verfasserin aut Enthalten in Breast cancer research BioMed Central, 1999 6(2004), 5 vom: 29. Juli (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:6 year:2004 number:5 day:29 month:07 https://dx.doi.org/10.1186/bcr912 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 VZ AR 6 2004 5 29 07 |
| spelling |
10.1186/bcr912 doi (DE-627)SPR029921619 (SPR)bcr912-e DE-627 ger DE-627 rakwb eng 610 VZ 44.00 bkl Vestey, SB verfasserin aut $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. ARF protein (dpeaa)DE-He213 ductal carcinoma (dpeaa)DE-He213 Hdm2 (dpeaa)DE-He213 HER-2 (dpeaa)DE-He213 immunohistochemistry (dpeaa)DE-He213 Sen, C verfasserin aut Calder, CJ verfasserin aut Perks, CM verfasserin aut Pignatelli, M verfasserin aut Winters, ZE verfasserin aut Enthalten in Breast cancer research BioMed Central, 1999 6(2004), 5 vom: 29. Juli (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:6 year:2004 number:5 day:29 month:07 https://dx.doi.org/10.1186/bcr912 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 VZ AR 6 2004 5 29 07 |
| allfields_unstemmed |
10.1186/bcr912 doi (DE-627)SPR029921619 (SPR)bcr912-e DE-627 ger DE-627 rakwb eng 610 VZ 44.00 bkl Vestey, SB verfasserin aut $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. ARF protein (dpeaa)DE-He213 ductal carcinoma (dpeaa)DE-He213 Hdm2 (dpeaa)DE-He213 HER-2 (dpeaa)DE-He213 immunohistochemistry (dpeaa)DE-He213 Sen, C verfasserin aut Calder, CJ verfasserin aut Perks, CM verfasserin aut Pignatelli, M verfasserin aut Winters, ZE verfasserin aut Enthalten in Breast cancer research BioMed Central, 1999 6(2004), 5 vom: 29. Juli (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:6 year:2004 number:5 day:29 month:07 https://dx.doi.org/10.1186/bcr912 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 VZ AR 6 2004 5 29 07 |
| allfieldsGer |
10.1186/bcr912 doi (DE-627)SPR029921619 (SPR)bcr912-e DE-627 ger DE-627 rakwb eng 610 VZ 44.00 bkl Vestey, SB verfasserin aut $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. ARF protein (dpeaa)DE-He213 ductal carcinoma (dpeaa)DE-He213 Hdm2 (dpeaa)DE-He213 HER-2 (dpeaa)DE-He213 immunohistochemistry (dpeaa)DE-He213 Sen, C verfasserin aut Calder, CJ verfasserin aut Perks, CM verfasserin aut Pignatelli, M verfasserin aut Winters, ZE verfasserin aut Enthalten in Breast cancer research BioMed Central, 1999 6(2004), 5 vom: 29. Juli (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:6 year:2004 number:5 day:29 month:07 https://dx.doi.org/10.1186/bcr912 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 VZ AR 6 2004 5 29 07 |
| allfieldsSound |
10.1186/bcr912 doi (DE-627)SPR029921619 (SPR)bcr912-e DE-627 ger DE-627 rakwb eng 610 VZ 44.00 bkl Vestey, SB verfasserin aut $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 2004 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. ARF protein (dpeaa)DE-He213 ductal carcinoma (dpeaa)DE-He213 Hdm2 (dpeaa)DE-He213 HER-2 (dpeaa)DE-He213 immunohistochemistry (dpeaa)DE-He213 Sen, C verfasserin aut Calder, CJ verfasserin aut Perks, CM verfasserin aut Pignatelli, M verfasserin aut Winters, ZE verfasserin aut Enthalten in Breast cancer research BioMed Central, 1999 6(2004), 5 vom: 29. Juli (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:6 year:2004 number:5 day:29 month:07 https://dx.doi.org/10.1186/bcr912 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 VZ AR 6 2004 5 29 07 |
| language |
English |
| source |
Enthalten in Breast cancer research 6(2004), 5 vom: 29. Juli volume:6 year:2004 number:5 day:29 month:07 |
| sourceStr |
Enthalten in Breast cancer research 6(2004), 5 vom: 29. Juli volume:6 year:2004 number:5 day:29 month:07 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
ARF protein ductal carcinoma Hdm2 HER-2 immunohistochemistry |
| dewey-raw |
610 |
| isfreeaccess_bool |
false |
| container_title |
Breast cancer research |
| authorswithroles_txt_mv |
Vestey, SB @@aut@@ Sen, C @@aut@@ Calder, CJ @@aut@@ Perks, CM @@aut@@ Pignatelli, M @@aut@@ Winters, ZE @@aut@@ |
| publishDateDaySort_date |
2004-07-29T00:00:00Z |
| hierarchy_top_id |
326645950 |
| dewey-sort |
3610 |
| id |
SPR029921619 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR029921619</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240426065201.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2004 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/bcr912</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR029921619</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)bcr912-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Vestey, SB</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2004</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ARF protein</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ductal carcinoma</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hdm2</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HER-2</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">immunohistochemistry</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sen, C</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Calder, CJ</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Perks, CM</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pignatelli, M</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Winters, ZE</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Breast cancer research</subfield><subfield code="d">BioMed Central, 1999</subfield><subfield code="g">6(2004), 5 vom: 29. Juli</subfield><subfield code="w">(DE-627)326645950</subfield><subfield code="w">(DE-600)2041618-0</subfield><subfield code="x">1465-542X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:6</subfield><subfield code="g">year:2004</subfield><subfield code="g">number:5</subfield><subfield code="g">day:29</subfield><subfield code="g">month:07</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/bcr912</subfield><subfield code="m">X:SPRINGER</subfield><subfield code="x">Resolving-System</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_0</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.00</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">6</subfield><subfield code="j">2004</subfield><subfield code="e">5</subfield><subfield code="b">29</subfield><subfield code="c">07</subfield></datafield></record></collection>
|
| author |
Vestey, SB |
| spellingShingle |
Vestey, SB ddc 610 bkl 44.00 misc ARF protein misc ductal carcinoma misc Hdm2 misc HER-2 misc immunohistochemistry $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 |
| authorStr |
Vestey, SB |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)326645950 |
| format |
electronic Article |
| dewey-ones |
610 - Medicine & health |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut |
| collection |
springer |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
1465-542X |
| topic_title |
610 VZ 44.00 bkl $ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 ARF protein (dpeaa)DE-He213 ductal carcinoma (dpeaa)DE-He213 Hdm2 (dpeaa)DE-He213 HER-2 (dpeaa)DE-He213 immunohistochemistry (dpeaa)DE-He213 |
| topic |
ddc 610 bkl 44.00 misc ARF protein misc ductal carcinoma misc Hdm2 misc HER-2 misc immunohistochemistry |
| topic_unstemmed |
ddc 610 bkl 44.00 misc ARF protein misc ductal carcinoma misc Hdm2 misc HER-2 misc immunohistochemistry |
| topic_browse |
ddc 610 bkl 44.00 misc ARF protein misc ductal carcinoma misc Hdm2 misc HER-2 misc immunohistochemistry |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
Breast cancer research |
| hierarchy_parent_id |
326645950 |
| dewey-tens |
610 - Medicine & health |
| hierarchy_top_title |
Breast cancer research |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)326645950 (DE-600)2041618-0 |
| title |
$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 |
| ctrlnum |
(DE-627)SPR029921619 (SPR)bcr912-e |
| title_full |
$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 |
| author_sort |
Vestey, SB |
| journal |
Breast cancer research |
| journalStr |
Breast cancer research |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology |
| recordtype |
marc |
| publishDateSort |
2004 |
| contenttype_str_mv |
txt |
| author_browse |
Vestey, SB Sen, C Calder, CJ Perks, CM Pignatelli, M Winters, ZE |
| container_volume |
6 |
| class |
610 VZ 44.00 bkl |
| format_se |
Elektronische Aufsätze |
| author-letter |
Vestey, SB |
| doi_str_mv |
10.1186/bcr912 |
| dewey-full |
610 |
| author2-role |
verfasserin |
| title_sort |
$ p14^{arf} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and hdm2 |
| title_auth |
$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 |
| abstract |
Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
| abstractGer |
Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
| abstract_unstemmed |
Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications. © Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
| collection_details |
SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
| container_issue |
5 |
| title_short |
$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2 |
| url |
https://dx.doi.org/10.1186/bcr912 |
| remote_bool |
true |
| author2 |
Sen, C Calder, CJ Perks, CM Pignatelli, M Winters, ZE |
| author2Str |
Sen, C Calder, CJ Perks, CM Pignatelli, M Winters, ZE |
| ppnlink |
326645950 |
| mediatype_str_mv |
c |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| doi_str |
10.1186/bcr912 |
| up_date |
2024-07-04T02:42:23.389Z |
| _version_ |
1803614623778209792 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR029921619</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240426065201.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2004 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/bcr912</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR029921619</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)bcr912-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Vestey, SB</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">$ p14^{ARF} $ expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2004</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Vestey et al.; licensee BioMed Central Ltd. 2004. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction $ p14^{ARF} $ stabilises nuclear p53, with a variable expression of $ p14^{ARF} $ mRNA in breast cancers. In vitro, nuclear $ p14^{ARF} $ binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. $ p14^{ARF} $ is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of $ p14^{ARF} $ protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic $ p14^{ARF} $, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the $ p14^{ARF} $/Hdm2 pathway to inactivate $ p14^{ARF} $ and to influence Hdm2 activity and localisation. This study examined $ p14^{ARF} $ and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. Methods The 4C6 anti-$ p14^{ARF} $ monoclonal antibody and Dako Envision Plus system were used to evaluate $ p14^{ARF} $ expression in 103 patients; p53/Hdm2 staining was performed. Results $ p14^{ARF} $ was evaluable in 96 patients, with nuclear $ p14^{ARF} $ expression (modified Quick-score ≥ 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic $ p14^{ARF} $ was detectable in 23 breast cancers. Nuclear and cytoplasmic $ p14^{ARF} $ showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic $ p14^{ARF} $ were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic $ p14^{ARF} $ might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear $ p14^{ARF} $ (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). Conclusions Nuclear $ p14^{ARF} $ expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear $ p14^{ARF} $ and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of $ p14^{ARF} $/Hdm2 and p53 pathways in which consideration of cytoplasmic $ p14^{ARF} $ and Hdm2 might have tumorigenic implications.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ARF protein</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ductal carcinoma</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hdm2</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HER-2</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">immunohistochemistry</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sen, C</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Calder, CJ</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Perks, CM</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pignatelli, M</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Winters, ZE</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Breast cancer research</subfield><subfield code="d">BioMed Central, 1999</subfield><subfield code="g">6(2004), 5 vom: 29. Juli</subfield><subfield code="w">(DE-627)326645950</subfield><subfield code="w">(DE-600)2041618-0</subfield><subfield code="x">1465-542X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:6</subfield><subfield code="g">year:2004</subfield><subfield code="g">number:5</subfield><subfield code="g">day:29</subfield><subfield code="g">month:07</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/bcr912</subfield><subfield code="m">X:SPRINGER</subfield><subfield code="x">Resolving-System</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_0</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.00</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">6</subfield><subfield code="j">2004</subfield><subfield code="e">5</subfield><subfield code="b">29</subfield><subfield code="c">07</subfield></datafield></record></collection>
|
| score |
7.398505 |