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The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer

In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription f...

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Autores principales: Sharma, Naomi L., Massie, Charlie E., Butter, Falk, Mann, Matthias, Bon, Helene, Ramos-Montoya, Antonio, Menon, Suraj, Stark, Rory, Lamb, Alastair D., Scott, Helen E., Warren, Anne Y., Neal, David E., Mills, Ian G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041454/
https://www.ncbi.nlm.nih.gov/pubmed/24753418
http://dx.doi.org/10.1093/nar/gku281
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author Sharma, Naomi L.
Massie, Charlie E.
Butter, Falk
Mann, Matthias
Bon, Helene
Ramos-Montoya, Antonio
Menon, Suraj
Stark, Rory
Lamb, Alastair D.
Scott, Helen E.
Warren, Anne Y.
Neal, David E.
Mills, Ian G.
author_facet Sharma, Naomi L.
Massie, Charlie E.
Butter, Falk
Mann, Matthias
Bon, Helene
Ramos-Montoya, Antonio
Menon, Suraj
Stark, Rory
Lamb, Alastair D.
Scott, Helen E.
Warren, Anne Y.
Neal, David E.
Mills, Ian G.
author_sort Sharma, Naomi L.
collection PubMed
description In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention.
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spelling pubmed-40414542014-06-11 The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer Sharma, Naomi L. Massie, Charlie E. Butter, Falk Mann, Matthias Bon, Helene Ramos-Montoya, Antonio Menon, Suraj Stark, Rory Lamb, Alastair D. Scott, Helen E. Warren, Anne Y. Neal, David E. Mills, Ian G. Nucleic Acids Res Gene regulation, Chromatin and Epigenetics In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention. Oxford University Press 2014-06-01 2014-04-21 /pmc/articles/PMC4041454/ /pubmed/24753418 http://dx.doi.org/10.1093/nar/gku281 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Sharma, Naomi L.
Massie, Charlie E.
Butter, Falk
Mann, Matthias
Bon, Helene
Ramos-Montoya, Antonio
Menon, Suraj
Stark, Rory
Lamb, Alastair D.
Scott, Helen E.
Warren, Anne Y.
Neal, David E.
Mills, Ian G.
The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
title The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
title_full The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
title_fullStr The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
title_full_unstemmed The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
title_short The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
title_sort ets family member gabpα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041454/
https://www.ncbi.nlm.nih.gov/pubmed/24753418
http://dx.doi.org/10.1093/nar/gku281
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