The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells

Androgen receptor (AR) is involved in the development and progression of prostate cancers. However, the mechanisms by which this occurs remain incompletely understood. In previous reports, chicken ovalbumin upstream promoter-transcription factor II (COUP-TF II) has been suggested to play a role in t...

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Main Authors: Song, Chin-Hee, Lee, Hyun Joo, Park, Eunsook, Lee, Keesook
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492188/
id pubmed-3492188
recordtype oai_dc
spelling pubmed-34921882012-11-09 The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells Song, Chin-Hee Lee, Hyun Joo Park, Eunsook Lee, Keesook Research Article Androgen receptor (AR) is involved in the development and progression of prostate cancers. However, the mechanisms by which this occurs remain incompletely understood. In previous reports, chicken ovalbumin upstream promoter-transcription factor II (COUP-TF II) has been suggested to play a role in the development of cancers. In the present study, we explored a putative role of COUP-TF II in prostate cancers by investigating its effect on cell proliferation and a cross-talk between COUP-TF II and AR. Overexpression of COUP-TF II results in the inhibition of androgen-dependent proliferation of prostate cancer cells. Further studies show that COUP-TF II functions as a corepressor of AR. It represses AR transactivation on target promoters containing the androgen response element (ARE) in a dose-dependent manner. In addition, COUP-TF II interacts physically with AR in vitro and in vivo. It binds to both the DNA binding domain (DBD) and the ligand-binding domain (LBD) of AR and disrupts the N/C terminal interaction of AR. Furthermore, COUP-TF II competes with coactivators such as ARA70, SRC-1, and GRIP1 to modulate AR transactivation as well as inhibiting the recruitment of AR to its ARE-containing target promoter. Taken together, our findings suggest that COUP-TF II is a novel corepressor of AR, and provide an insight into the role of COUP-TF II in prostate cancers. Public Library of Science 2012-11-07 /pmc/articles/PMC3492188/ /pubmed/23145053 http://dx.doi.org/10.1371/journal.pone.0049026 Text en © 2012 Song et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Song, Chin-Hee
Lee, Hyun Joo
Park, Eunsook
Lee, Keesook
spellingShingle Song, Chin-Hee
Lee, Hyun Joo
Park, Eunsook
Lee, Keesook
The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells
author_facet Song, Chin-Hee
Lee, Hyun Joo
Park, Eunsook
Lee, Keesook
author_sort Song, Chin-Hee
title The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells
title_short The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells
title_full The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells
title_fullStr The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells
title_full_unstemmed The Chicken Ovalbumin Upstream Promoter-Transcription Factor II Negatively Regulates the Transactivation of Androgen Receptor in Prostate Cancer Cells
title_sort chicken ovalbumin upstream promoter-transcription factor ii negatively regulates the transactivation of androgen receptor in prostate cancer cells
description Androgen receptor (AR) is involved in the development and progression of prostate cancers. However, the mechanisms by which this occurs remain incompletely understood. In previous reports, chicken ovalbumin upstream promoter-transcription factor II (COUP-TF II) has been suggested to play a role in the development of cancers. In the present study, we explored a putative role of COUP-TF II in prostate cancers by investigating its effect on cell proliferation and a cross-talk between COUP-TF II and AR. Overexpression of COUP-TF II results in the inhibition of androgen-dependent proliferation of prostate cancer cells. Further studies show that COUP-TF II functions as a corepressor of AR. It represses AR transactivation on target promoters containing the androgen response element (ARE) in a dose-dependent manner. In addition, COUP-TF II interacts physically with AR in vitro and in vivo. It binds to both the DNA binding domain (DBD) and the ligand-binding domain (LBD) of AR and disrupts the N/C terminal interaction of AR. Furthermore, COUP-TF II competes with coactivators such as ARA70, SRC-1, and GRIP1 to modulate AR transactivation as well as inhibiting the recruitment of AR to its ARE-containing target promoter. Taken together, our findings suggest that COUP-TF II is a novel corepressor of AR, and provide an insight into the role of COUP-TF II in prostate cancers.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492188/
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