Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.

Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an...

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Autores principales:	Ruth Perets, Tommy Kaplan, Ilan Stein, Guy Hidas, Shay Tayeb, Eti Avraham, Yinon Ben-Neriah, Itamar Simon, Eli Pikarsky
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98d51e6f809f4a7db62300eaf6ecb0c3
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spelling	oai:doaj.org-article:98d51e6f809f4a7db62300eaf6ecb0c32021-11-18T08:13:14ZGenome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.1932-620310.1371/journal.pone.0046467https://doaj.org/article/98d51e6f809f4a7db62300eaf6ecb0c32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056316/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR - COUP-TF1 - which could possibly play a role in human prostate cancer.Ruth PeretsTommy KaplanIlan SteinGuy HidasShay TayebEti AvrahamYinon Ben-NeriahItamar SimonEli PikarskyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e46467 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ruth Perets Tommy Kaplan Ilan Stein Guy Hidas Shay Tayeb Eti Avraham Yinon Ben-Neriah Itamar Simon Eli Pikarsky Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.
description	Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR - COUP-TF1 - which could possibly play a role in human prostate cancer.
format	article
author	Ruth Perets Tommy Kaplan Ilan Stein Guy Hidas Shay Tayeb Eti Avraham Yinon Ben-Neriah Itamar Simon Eli Pikarsky
author_facet	Ruth Perets Tommy Kaplan Ilan Stein Guy Hidas Shay Tayeb Eti Avraham Yinon Ben-Neriah Itamar Simon Eli Pikarsky
author_sort	Ruth Perets
title	Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.
title_short	Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.
title_full	Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.
title_fullStr	Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.
title_full_unstemmed	Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.
title_sort	genome-wide analysis of androgen receptor targets reveals coup-tf1 as a novel player in human prostate cancer.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/98d51e6f809f4a7db62300eaf6ecb0c3
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Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.

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