Androgen Receptor Regulates a Distinct Transcription Program in Androgen-Independent Prostate Cancer
The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent targe...
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| Veröffentlicht in: | Cell 2009-07, Vol.138 (2), p.245-256 |
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| creator | Wang, Qianben Li, Wei Zhang, Yong Yuan, Xin Xu, Kexin Yu, Jindan Chen, Zhong Beroukhim, Rameen Wang, Hongyun Lupien, Mathieu Wu, Tao Regan, Meredith M. Meyer, Clifford A. Carroll, Jason S. Manrai, Arjun Kumar Jänne, Olli A. Balk, Steven P. Mehra, Rohit Han, Bo Chinnaiyan, Arul M. Rubin, Mark A. True, Lawrence Fiorentino, Michelangelo Fiore, Christopher Loda, Massimo Kantoff, Philip W. Liu, X. Shirley Brown, Myles |
| description | The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including
UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth. |
| doi_str_mv | 10.1016/j.cell.2009.04.056 |
| format | Article |
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UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2009.04.056</identifier><identifier>PMID: 19632176</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Androgens - metabolism ; Cell Division ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hepatocyte Nuclear Factor 3-alpha - metabolism ; Histones - metabolism ; Humans ; HUMDISEASE ; Male ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Receptors, Androgen - metabolism ; Transcriptional Activation ; Ubiquitin-Conjugating Enzymes - metabolism</subject><ispartof>Cell, 2009-07, Vol.138 (2), p.245-256</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-c9dbb165aace57fa4422d67368168c153e3816514b5d69d3783d37fbe63b9ccd3</citedby><cites>FETCH-LOGICAL-c484t-c9dbb165aace57fa4422d67368168c153e3816514b5d69d3783d37fbe63b9ccd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0092867409005170$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19632176$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Qianben</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Yuan, Xin</creatorcontrib><creatorcontrib>Xu, Kexin</creatorcontrib><creatorcontrib>Yu, Jindan</creatorcontrib><creatorcontrib>Chen, Zhong</creatorcontrib><creatorcontrib>Beroukhim, Rameen</creatorcontrib><creatorcontrib>Wang, Hongyun</creatorcontrib><creatorcontrib>Lupien, Mathieu</creatorcontrib><creatorcontrib>Wu, Tao</creatorcontrib><creatorcontrib>Regan, Meredith M.</creatorcontrib><creatorcontrib>Meyer, Clifford A.</creatorcontrib><creatorcontrib>Carroll, Jason S.</creatorcontrib><creatorcontrib>Manrai, Arjun Kumar</creatorcontrib><creatorcontrib>Jänne, Olli A.</creatorcontrib><creatorcontrib>Balk, Steven P.</creatorcontrib><creatorcontrib>Mehra, Rohit</creatorcontrib><creatorcontrib>Han, Bo</creatorcontrib><creatorcontrib>Chinnaiyan, Arul M.</creatorcontrib><creatorcontrib>Rubin, Mark A.</creatorcontrib><creatorcontrib>True, Lawrence</creatorcontrib><creatorcontrib>Fiorentino, Michelangelo</creatorcontrib><creatorcontrib>Fiore, Christopher</creatorcontrib><creatorcontrib>Loda, Massimo</creatorcontrib><creatorcontrib>Kantoff, Philip W.</creatorcontrib><creatorcontrib>Liu, X. Shirley</creatorcontrib><creatorcontrib>Brown, Myles</creatorcontrib><title>Androgen Receptor Regulates a Distinct Transcription Program in Androgen-Independent Prostate Cancer</title><title>Cell</title><addtitle>Cell</addtitle><description>The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including
UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.</description><subject>Androgens - metabolism</subject><subject>Cell Division</subject><subject>Cell Line, Tumor</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hepatocyte Nuclear Factor 3-alpha - metabolism</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>HUMDISEASE</subject><subject>Male</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Receptors, Androgen - metabolism</subject><subject>Transcriptional Activation</subject><subject>Ubiquitin-Conjugating Enzymes - metabolism</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctq3DAUFaGlmSb9gSyKV93Z1Vs2lEKYpG0gkBDStZClO1MNHtmVNIH8fWRmmrSbdHN14Ty4OgehM4Ibgon8vGksDENDMe4azBss5BFaENypmhNF36BFAWjdSsWP0fuUNhjjVgjxDh2TTjJKlFwgdx5cHNcQqjuwMOUxlmW9G0yGVJnqwqfsg83VfTQh2ein7MdQ3RZJNNvKh-qPvr4KDiYoI-QZT7lYVEsTLMRT9HZlhgQfDu8J-vnt8n75o76--X61PL-uLW95rm3n-p5IYYwFoVaGc0qdVEy2RLaWCAasbILwXjjZOaZaVsaqB8n6zlrHTtDXve-067fgbDklmkFP0W9NfNSj8fpfJPhfej0-aKqobKkqBp8OBnH8vYOU9danOWQTYNwlLZUgirX8v0RKsMQCy0Kke6ItkaQIq-drCNZzi3qjZ52eW9SY69JiEX38-x8vkkNthfBlT4CS5oOHqJP1UKJ2PoLN2o3-Nf8nd3ywlA</recordid><startdate>20090723</startdate><enddate>20090723</enddate><creator>Wang, Qianben</creator><creator>Li, Wei</creator><creator>Zhang, Yong</creator><creator>Yuan, Xin</creator><creator>Xu, Kexin</creator><creator>Yu, Jindan</creator><creator>Chen, Zhong</creator><creator>Beroukhim, Rameen</creator><creator>Wang, Hongyun</creator><creator>Lupien, Mathieu</creator><creator>Wu, Tao</creator><creator>Regan, Meredith M.</creator><creator>Meyer, Clifford A.</creator><creator>Carroll, Jason S.</creator><creator>Manrai, Arjun Kumar</creator><creator>Jänne, Olli A.</creator><creator>Balk, Steven P.</creator><creator>Mehra, Rohit</creator><creator>Han, Bo</creator><creator>Chinnaiyan, Arul M.</creator><creator>Rubin, Mark A.</creator><creator>True, Lawrence</creator><creator>Fiorentino, Michelangelo</creator><creator>Fiore, Christopher</creator><creator>Loda, Massimo</creator><creator>Kantoff, Philip W.</creator><creator>Liu, X. 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Shirley</creatorcontrib><creatorcontrib>Brown, Myles</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Qianben</au><au>Li, Wei</au><au>Zhang, Yong</au><au>Yuan, Xin</au><au>Xu, Kexin</au><au>Yu, Jindan</au><au>Chen, Zhong</au><au>Beroukhim, Rameen</au><au>Wang, Hongyun</au><au>Lupien, Mathieu</au><au>Wu, Tao</au><au>Regan, Meredith M.</au><au>Meyer, Clifford A.</au><au>Carroll, Jason S.</au><au>Manrai, Arjun Kumar</au><au>Jänne, Olli A.</au><au>Balk, Steven P.</au><au>Mehra, Rohit</au><au>Han, Bo</au><au>Chinnaiyan, Arul M.</au><au>Rubin, Mark A.</au><au>True, Lawrence</au><au>Fiorentino, Michelangelo</au><au>Fiore, Christopher</au><au>Loda, Massimo</au><au>Kantoff, Philip W.</au><au>Liu, X. Shirley</au><au>Brown, Myles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Androgen Receptor Regulates a Distinct Transcription Program in Androgen-Independent Prostate Cancer</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2009-07-23</date><risdate>2009</risdate><volume>138</volume><issue>2</issue><spage>245</spage><epage>256</epage><pages>245-256</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including
UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19632176</pmid><doi>10.1016/j.cell.2009.04.056</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Androgens - metabolism Cell Division Cell Line, Tumor Gene Expression Regulation, Neoplastic Hepatocyte Nuclear Factor 3-alpha - metabolism Histones - metabolism Humans HUMDISEASE Male Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Receptors, Androgen - metabolism Transcriptional Activation Ubiquitin-Conjugating Enzymes - metabolism |
| title | Androgen Receptor Regulates a Distinct Transcription Program in Androgen-Independent Prostate Cancer |
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