Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells
Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Cheadle, Chris [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2008 |
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| Schlagwörter: |
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| Anmerkung: |
© Cheadle et al; licensee BioMed Central Ltd. 2008 |
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| Übergeordnetes Werk: |
Enthalten in: BMC medical genomics - London : BioMed Central, 2008, 1(2008), 1 vom: 26. Sept. |
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| Übergeordnetes Werk: |
volume:1 ; year:2008 ; number:1 ; day:26 ; month:09 |
| Links: |
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| DOI / URN: |
10.1186/1755-8794-1-43 |
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| Katalog-ID: |
SPR028464680 |
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| 520 | |a Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. | ||
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| 650 | 4 | |a Ovarian Cancer Cell Line |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a OVCAR Cell |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Peritoneal Malignant Mesothelioma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Diffuse Peritoneal Malignant Mesothelioma |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Nesterova, Maria |4 aut | |
| 700 | 1 | |a Watkins, Tonya |4 aut | |
| 700 | 1 | |a Barnes, Kathleen C |4 aut | |
| 700 | 1 | |a Hall, John C |4 aut | |
| 700 | 1 | |a Rosen, Antony |4 aut | |
| 700 | 1 | |a Becker, Kevin G |4 aut | |
| 700 | 1 | |a Cho-Chung, Yoon S |4 aut | |
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10.1186/1755-8794-1-43 doi (DE-627)SPR028464680 (SPR)1755-8794-1-43-e DE-627 ger DE-627 rakwb eng Cheadle, Chris verfasserin aut Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cheadle et al; licensee BioMed Central Ltd. 2008 Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. Ovarian Cancer Cell (dpeaa)DE-He213 Ovarian Cancer Cell Line (dpeaa)DE-He213 OVCAR Cell (dpeaa)DE-He213 Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Diffuse Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Nesterova, Maria aut Watkins, Tonya aut Barnes, Kathleen C aut Hall, John C aut Rosen, Antony aut Becker, Kevin G aut Cho-Chung, Yoon S aut Enthalten in BMC medical genomics London : BioMed Central, 2008 1(2008), 1 vom: 26. Sept. (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:1 year:2008 number:1 day:26 month:09 https://dx.doi.org/10.1186/1755-8794-1-43 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_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 AR 1 2008 1 26 09 |
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10.1186/1755-8794-1-43 doi (DE-627)SPR028464680 (SPR)1755-8794-1-43-e DE-627 ger DE-627 rakwb eng Cheadle, Chris verfasserin aut Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cheadle et al; licensee BioMed Central Ltd. 2008 Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. Ovarian Cancer Cell (dpeaa)DE-He213 Ovarian Cancer Cell Line (dpeaa)DE-He213 OVCAR Cell (dpeaa)DE-He213 Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Diffuse Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Nesterova, Maria aut Watkins, Tonya aut Barnes, Kathleen C aut Hall, John C aut Rosen, Antony aut Becker, Kevin G aut Cho-Chung, Yoon S aut Enthalten in BMC medical genomics London : BioMed Central, 2008 1(2008), 1 vom: 26. Sept. (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:1 year:2008 number:1 day:26 month:09 https://dx.doi.org/10.1186/1755-8794-1-43 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_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 AR 1 2008 1 26 09 |
| allfields_unstemmed |
10.1186/1755-8794-1-43 doi (DE-627)SPR028464680 (SPR)1755-8794-1-43-e DE-627 ger DE-627 rakwb eng Cheadle, Chris verfasserin aut Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cheadle et al; licensee BioMed Central Ltd. 2008 Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. Ovarian Cancer Cell (dpeaa)DE-He213 Ovarian Cancer Cell Line (dpeaa)DE-He213 OVCAR Cell (dpeaa)DE-He213 Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Diffuse Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Nesterova, Maria aut Watkins, Tonya aut Barnes, Kathleen C aut Hall, John C aut Rosen, Antony aut Becker, Kevin G aut Cho-Chung, Yoon S aut Enthalten in BMC medical genomics London : BioMed Central, 2008 1(2008), 1 vom: 26. Sept. (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:1 year:2008 number:1 day:26 month:09 https://dx.doi.org/10.1186/1755-8794-1-43 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_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 AR 1 2008 1 26 09 |
| allfieldsGer |
10.1186/1755-8794-1-43 doi (DE-627)SPR028464680 (SPR)1755-8794-1-43-e DE-627 ger DE-627 rakwb eng Cheadle, Chris verfasserin aut Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cheadle et al; licensee BioMed Central Ltd. 2008 Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. Ovarian Cancer Cell (dpeaa)DE-He213 Ovarian Cancer Cell Line (dpeaa)DE-He213 OVCAR Cell (dpeaa)DE-He213 Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Diffuse Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Nesterova, Maria aut Watkins, Tonya aut Barnes, Kathleen C aut Hall, John C aut Rosen, Antony aut Becker, Kevin G aut Cho-Chung, Yoon S aut Enthalten in BMC medical genomics London : BioMed Central, 2008 1(2008), 1 vom: 26. Sept. (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:1 year:2008 number:1 day:26 month:09 https://dx.doi.org/10.1186/1755-8794-1-43 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_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 AR 1 2008 1 26 09 |
| allfieldsSound |
10.1186/1755-8794-1-43 doi (DE-627)SPR028464680 (SPR)1755-8794-1-43-e DE-627 ger DE-627 rakwb eng Cheadle, Chris verfasserin aut Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cheadle et al; licensee BioMed Central Ltd. 2008 Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. Ovarian Cancer Cell (dpeaa)DE-He213 Ovarian Cancer Cell Line (dpeaa)DE-He213 OVCAR Cell (dpeaa)DE-He213 Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Diffuse Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Nesterova, Maria aut Watkins, Tonya aut Barnes, Kathleen C aut Hall, John C aut Rosen, Antony aut Becker, Kevin G aut Cho-Chung, Yoon S aut Enthalten in BMC medical genomics London : BioMed Central, 2008 1(2008), 1 vom: 26. Sept. (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:1 year:2008 number:1 day:26 month:09 https://dx.doi.org/10.1186/1755-8794-1-43 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_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 AR 1 2008 1 26 09 |
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Cheadle, Chris |
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Cheadle, Chris misc Ovarian Cancer Cell misc Ovarian Cancer Cell Line misc OVCAR Cell misc Peritoneal Malignant Mesothelioma misc Diffuse Peritoneal Malignant Mesothelioma Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells |
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Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells Ovarian Cancer Cell (dpeaa)DE-He213 Ovarian Cancer Cell Line (dpeaa)DE-He213 OVCAR Cell (dpeaa)DE-He213 Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 Diffuse Peritoneal Malignant Mesothelioma (dpeaa)DE-He213 |
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misc Ovarian Cancer Cell misc Ovarian Cancer Cell Line misc OVCAR Cell misc Peritoneal Malignant Mesothelioma misc Diffuse Peritoneal Malignant Mesothelioma |
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misc Ovarian Cancer Cell misc Ovarian Cancer Cell Line misc OVCAR Cell misc Peritoneal Malignant Mesothelioma misc Diffuse Peritoneal Malignant Mesothelioma |
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misc Ovarian Cancer Cell misc Ovarian Cancer Cell Line misc OVCAR Cell misc Peritoneal Malignant Mesothelioma misc Diffuse Peritoneal Malignant Mesothelioma |
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regulatory subunits of pka define an axis of cellular proliferation/differentiation in ovarian cancer cells |
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Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells |
| abstract |
Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. © Cheadle et al; licensee BioMed Central Ltd. 2008 |
| abstractGer |
Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. © Cheadle et al; licensee BioMed Central Ltd. 2008 |
| abstract_unstemmed |
Background The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression. © Cheadle et al; licensee BioMed Central Ltd. 2008 |
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Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8). Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ovarian Cancer Cell</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ovarian Cancer Cell Line</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">OVCAR Cell</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Peritoneal Malignant Mesothelioma</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Diffuse Peritoneal Malignant Mesothelioma</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nesterova, Maria</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Watkins, Tonya</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Barnes, Kathleen C</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hall, John C</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rosen, Antony</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Becker, Kevin G</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Cho-Chung, Yoon S</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">BMC medical genomics</subfield><subfield code="d">London : BioMed Central, 2008</subfield><subfield code="g">1(2008), 1 vom: 26. 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