Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines

Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with de...
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Autor*in:	Zhang, Xi [verfasserIn] Hofmann, Simone [verfasserIn] Harbeck, Nadia [verfasserIn] Jeschke, Udo [verfasserIn] Sixou, Sophie [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Übergeordnetes Werk:	Enthalten in: Drugs in R & D - [S.l.] : Springer International, 1999, 17(2017), 4 vom: 06. Sept., Seite 569-583
Übergeordnetes Werk:	volume:17 ; year:2017 ; number:4 ; day:06 ; month:09 ; pages:569-583

Links:	Volltext

DOI / URN:	10.1007/s40268-017-0208-6

Katalog-ID:	SPR033296235

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520			\|a Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies.
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author_variant	x z xz s h sh n h nh u j uj s s ss
matchkey_str	article:11796901:2017----::matftpsdobc1xrsinnaiubes
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allfields	10.1007/s40268-017-0208-6 doi (DE-627)SPR033296235 (SPR)s40268-017-0208-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Zhang, Xi verfasserin aut Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies. Hofmann, Simone verfasserin aut Harbeck, Nadia verfasserin aut Jeschke, Udo verfasserin aut Sixou, Sophie verfasserin aut Enthalten in Drugs in R & D [S.l.] : Springer International, 1999 17(2017), 4 vom: 06. Sept., Seite 569-583 (DE-627)357171527 (DE-600)2094513-9 1179-6901 nnns volume:17 year:2017 number:4 day:06 month:09 pages:569-583 https://dx.doi.org/10.1007/s40268-017-0208-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 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 44.40 ASE AR 17 2017 4 06 09 569-583
spelling	10.1007/s40268-017-0208-6 doi (DE-627)SPR033296235 (SPR)s40268-017-0208-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Zhang, Xi verfasserin aut Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies. Hofmann, Simone verfasserin aut Harbeck, Nadia verfasserin aut Jeschke, Udo verfasserin aut Sixou, Sophie verfasserin aut Enthalten in Drugs in R & D [S.l.] : Springer International, 1999 17(2017), 4 vom: 06. Sept., Seite 569-583 (DE-627)357171527 (DE-600)2094513-9 1179-6901 nnns volume:17 year:2017 number:4 day:06 month:09 pages:569-583 https://dx.doi.org/10.1007/s40268-017-0208-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 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 44.40 ASE AR 17 2017 4 06 09 569-583
allfields_unstemmed	10.1007/s40268-017-0208-6 doi (DE-627)SPR033296235 (SPR)s40268-017-0208-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Zhang, Xi verfasserin aut Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies. Hofmann, Simone verfasserin aut Harbeck, Nadia verfasserin aut Jeschke, Udo verfasserin aut Sixou, Sophie verfasserin aut Enthalten in Drugs in R & D [S.l.] : Springer International, 1999 17(2017), 4 vom: 06. Sept., Seite 569-583 (DE-627)357171527 (DE-600)2094513-9 1179-6901 nnns volume:17 year:2017 number:4 day:06 month:09 pages:569-583 https://dx.doi.org/10.1007/s40268-017-0208-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 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 44.40 ASE AR 17 2017 4 06 09 569-583
allfieldsGer	10.1007/s40268-017-0208-6 doi (DE-627)SPR033296235 (SPR)s40268-017-0208-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Zhang, Xi verfasserin aut Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies. Hofmann, Simone verfasserin aut Harbeck, Nadia verfasserin aut Jeschke, Udo verfasserin aut Sixou, Sophie verfasserin aut Enthalten in Drugs in R & D [S.l.] : Springer International, 1999 17(2017), 4 vom: 06. Sept., Seite 569-583 (DE-627)357171527 (DE-600)2094513-9 1179-6901 nnns volume:17 year:2017 number:4 day:06 month:09 pages:569-583 https://dx.doi.org/10.1007/s40268-017-0208-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 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 44.40 ASE AR 17 2017 4 06 09 569-583
allfieldsSound	10.1007/s40268-017-0208-6 doi (DE-627)SPR033296235 (SPR)s40268-017-0208-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Zhang, Xi verfasserin aut Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies. Hofmann, Simone verfasserin aut Harbeck, Nadia verfasserin aut Jeschke, Udo verfasserin aut Sixou, Sophie verfasserin aut Enthalten in Drugs in R & D [S.l.] : Springer International, 1999 17(2017), 4 vom: 06. Sept., Seite 569-583 (DE-627)357171527 (DE-600)2094513-9 1179-6901 nnns volume:17 year:2017 number:4 day:06 month:09 pages:569-583 https://dx.doi.org/10.1007/s40268-017-0208-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2153 GBV_ILN_2190 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 44.40 ASE AR 17 2017 4 06 09 569-583
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title_sort	impact of etoposide on brca1 expression in various breast cancer cell lines
title_auth	Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines
abstract	Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies.
abstractGer	Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies.
abstract_unstemmed	Abstract Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. In addition, determination of early and late apoptosis helped to complete the analysis of BRCA1 functions in the DNA damage pathway of aggressive BC. In conclusion, our study suggested that high cytoplasmic BRCA1 protein levels could be considered as a potential predictive marker for response to chemotherapy in both sporadic and hereditary BC. Tumors with either BRCAness phenotype or germline BRCA1 mutation are both aggressive BCs associated with poor prognosis and could both be subjected to targeted therapies against BRCA1-mutated BC in future clinical management strategies.
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title_short	Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines
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author2	Hofmann, Simone Harbeck, Nadia Jeschke, Udo Sixou, Sophie
author2Str	Hofmann, Simone Harbeck, Nadia Jeschke, Udo Sixou, Sophie
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doi_str	10.1007/s40268-017-0208-6
up_date	2024-07-03T17:47:04.049Z
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BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called ‘BRCAness’. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers. In order to determine whether and how etoposide regulates the protein levels of BRCA1 in BC cells, we exposed a panel of five selected cell lines to etoposide, compared the results to untreated control cells, and then stained the cells with the specific, reliable, and reproducible MS110 antibody directed against phosphorylated Ser1423 BRCA1. By evaluating cytoplasmic BRCA1 protein levels, we were able to distinguish three aggressive BC subtypes with BRCAness characteristics. 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Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines

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