Repressive effects of resveratrol on androgen receptor transcriptional activity.
<h4>Background</h4>The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-10-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19816598/pdf/?tool=EBI |
| _version_ | 1818931737152978944 |
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| author | Wen-feng Shi Melanie Leong Ellen Cho Joseph Farrell Han-chun Chen Jun Tian Dianzheng Zhang |
| author_facet | Wen-feng Shi Melanie Leong Ellen Cho Joseph Farrell Han-chun Chen Jun Tian Dianzheng Zhang |
| author_sort | Wen-feng Shi |
| collection | DOAJ |
| description | <h4>Background</h4>The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity.<h4>Methodology</h4>The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of AR-negative HeLa cells to generate the AR(+) cells. The constitutively expressed AR was characterized by monitoring hormone-stimulated nuclear translocation, DNA binding, and transcriptional activation, with the AR(-) cells serving as controls. AR(+) cells were treated with RSV, and both AR protein levels and AR transcriptional activity were measured simultaneously. Chromatin immunoprecipitation (ChIP) assays were used to detect the effects of RSV on the recruitment of AR to its cognate element (ARE).<h4>Results</h4>AR in the AR (+) stable cell line functions in a manner similar to that of endogenously expressed AR. Using this model system we clearly demonstrated that RSV represses AR transcriptional activity independently of any effects on AR protein levels. However, neither the hormone-mediated nucleus translocation nor the AR/ARE interaction was affected by RSV treatment.<h4>Conclusion</h4>We demonstrated unambiguously that RSV regulates AR target gene expression, at least in part, by repressing AR transcriptional activity. Repressive effects of RSV on AR activity result from mechanisms other than the affects of AR nuclear translocation or DNA binding. |
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| id | doaj.art-05bca1c7635449a59580b4c50ec138cf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T04:21:21Z |
| publishDate | 2009-10-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-05bca1c7635449a59580b4c50ec138cf2022-12-21T19:53:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e739810.1371/journal.pone.0007398Repressive effects of resveratrol on androgen receptor transcriptional activity.Wen-feng ShiMelanie LeongEllen ChoJoseph FarrellHan-chun ChenJun TianDianzheng Zhang<h4>Background</h4>The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity.<h4>Methodology</h4>The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of AR-negative HeLa cells to generate the AR(+) cells. The constitutively expressed AR was characterized by monitoring hormone-stimulated nuclear translocation, DNA binding, and transcriptional activation, with the AR(-) cells serving as controls. AR(+) cells were treated with RSV, and both AR protein levels and AR transcriptional activity were measured simultaneously. Chromatin immunoprecipitation (ChIP) assays were used to detect the effects of RSV on the recruitment of AR to its cognate element (ARE).<h4>Results</h4>AR in the AR (+) stable cell line functions in a manner similar to that of endogenously expressed AR. Using this model system we clearly demonstrated that RSV represses AR transcriptional activity independently of any effects on AR protein levels. However, neither the hormone-mediated nucleus translocation nor the AR/ARE interaction was affected by RSV treatment.<h4>Conclusion</h4>We demonstrated unambiguously that RSV regulates AR target gene expression, at least in part, by repressing AR transcriptional activity. Repressive effects of RSV on AR activity result from mechanisms other than the affects of AR nuclear translocation or DNA binding.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19816598/pdf/?tool=EBI |
| spellingShingle | Wen-feng Shi Melanie Leong Ellen Cho Joseph Farrell Han-chun Chen Jun Tian Dianzheng Zhang Repressive effects of resveratrol on androgen receptor transcriptional activity. PLoS ONE |
| title | Repressive effects of resveratrol on androgen receptor transcriptional activity. |
| title_full | Repressive effects of resveratrol on androgen receptor transcriptional activity. |
| title_fullStr | Repressive effects of resveratrol on androgen receptor transcriptional activity. |
| title_full_unstemmed | Repressive effects of resveratrol on androgen receptor transcriptional activity. |
| title_short | Repressive effects of resveratrol on androgen receptor transcriptional activity. |
| title_sort | repressive effects of resveratrol on androgen receptor transcriptional activity |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19816598/pdf/?tool=EBI |
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