The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man

The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR...

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Published in:	Cancer cell Vol. 23; no. 1; p. 35
Main Authors:	Sharma, Naomi L, Massie, Charlie E, Ramos-Montoya, Antonio, Zecchini, Vincent, Scott, Helen E, Lamb, Alastair D, MacArthur, Stewart, Stark, Rory, Warren, Anne Y, Mills, Ian G, Neal, David E
Format:	Journal Article
Language:	English
Published:	United States 14.01.2013
Subjects:	Animals Binding Sites Cell Line, Tumor Gene Expression Regulation, Neoplastic Histones - metabolism Humans Male Mice Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Receptors, Androgen - metabolism Receptors, Androgen - physiology
ISSN:	1878-3686, 1878-3686
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Abstract	The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR binding sites in CRPC tissue, most of which were not identified in PC cell lines. Many adjacent genes showed AR regulation in xenografts but not in cultured LNCaPs, demonstrating an in-vivo-restricted set of AR-regulated genes. Functional studies support a model of altered signaling in vivo that directs AR binding. We identified a 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets, showing the importance of persistent AR signaling in CRPC.
AbstractList	The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR binding sites in CRPC tissue, most of which were not identified in PC cell lines. Many adjacent genes showed AR regulation in xenografts but not in cultured LNCaPs, demonstrating an in-vivo-restricted set of AR-regulated genes. Functional studies support a model of altered signaling in vivo that directs AR binding. We identified a 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets, showing the importance of persistent AR signaling in CRPC. The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR binding sites in CRPC tissue, most of which were not identified in PC cell lines. Many adjacent genes showed AR regulation in xenografts but not in cultured LNCaPs, demonstrating an in-vivo-restricted set of AR-regulated genes. Functional studies support a model of altered signaling in vivo that directs AR binding. We identified a 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets, showing the importance of persistent AR signaling in CRPC.The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR binding sites in CRPC tissue, most of which were not identified in PC cell lines. Many adjacent genes showed AR regulation in xenografts but not in cultured LNCaPs, demonstrating an in-vivo-restricted set of AR-regulated genes. Functional studies support a model of altered signaling in vivo that directs AR binding. We identified a 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets, showing the importance of persistent AR signaling in CRPC.
Author	Sharma, Naomi L MacArthur, Stewart Zecchini, Vincent Lamb, Alastair D Warren, Anne Y Ramos-Montoya, Antonio Massie, Charlie E Stark, Rory Scott, Helen E Mills, Ian G Neal, David E
Author_xml	– sequence: 1 givenname: Naomi L surname: Sharma fullname: Sharma, Naomi L organization: Uro-oncology Research Group, Cambridge Research Institute, Cambridge, UK – sequence: 2 givenname: Charlie E surname: Massie fullname: Massie, Charlie E – sequence: 3 givenname: Antonio surname: Ramos-Montoya fullname: Ramos-Montoya, Antonio – sequence: 4 givenname: Vincent surname: Zecchini fullname: Zecchini, Vincent – sequence: 5 givenname: Helen E surname: Scott fullname: Scott, Helen E – sequence: 6 givenname: Alastair D surname: Lamb fullname: Lamb, Alastair D – sequence: 7 givenname: Stewart surname: MacArthur fullname: MacArthur, Stewart – sequence: 8 givenname: Rory surname: Stark fullname: Stark, Rory – sequence: 9 givenname: Anne Y surname: Warren fullname: Warren, Anne Y – sequence: 10 givenname: Ian G surname: Mills fullname: Mills, Ian G – sequence: 11 givenname: David E surname: Neal fullname: Neal, David E
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23260764$$D View this record in MEDLINE/PubMed
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SubjectTerms	Animals Binding Sites Cell Line, Tumor Gene Expression Regulation, Neoplastic Histones - metabolism Humans Male Mice Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Receptors, Androgen - metabolism Receptors, Androgen - physiology
Title	The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man
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