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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Vydáno v:Cancer cell Ročník 23; číslo 1; s. 35
Hlavní autoři: 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 14.01.2013
Témata:
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
On-line přístup:Zjistit podrobnosti o přístupu
Tagy: Přidat tag
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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
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  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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PublicationDate 2013-01-14
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  year: 2013
  text: 2013-01-14
  day: 14
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PublicationTitle Cancer cell
PublicationTitleAlternate Cancer Cell
PublicationYear 2013
References 24253417 - Cancer Biol Ther. 2014 Jan;15(1):16-8. doi: 10.4161/cbt.27149.
References_xml – reference: 24253417 - Cancer Biol Ther. 2014 Jan;15(1):16-8. doi: 10.4161/cbt.27149.
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Snippet 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...
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StartPage 35
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
URI https://www.ncbi.nlm.nih.gov/pubmed/23260764
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