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

Naomi L Sharma; Charlie E Massie; Antonio Ramos-Montoya; Vincent Zecchini; Helen E Scott; Alastair D Lamb; Stewart MacArthur; Rory Stark; Anne Y Warren; Ian G Mills; David E Neal

doi:10.1016/j.ccr.2012.11.010

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

Naomi L Sharma
, Charlie E Massie
, Antonio Ramos-Montoya
, Vincent Zecchini
, Helen E Scott
, Alastair D Lamb
, Stewart MacArthur
, Rory Stark
, Anne Y Warren
, Ian G Mills
, David E Neal

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

351 Citations (Scopus)

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.

Original language	English
Pages (from-to)	35-47
Number of pages	13
Journal	Cancer Cell
Volume	23
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2012.11.010
Publication status	Published - 14 Jan 2013

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Animals
Binding Sites
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Histones
Humans
Male
Mice
Prostatic Neoplasms
Receptors, Androgen

Access to Document

10.1016/j.ccr.2012.11.010

Cite this

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title = "The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man",

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.",

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AU - Sharma, Naomi L

AU - Massie, Charlie E

AU - Ramos-Montoya, Antonio

AU - Zecchini, Vincent

AU - Scott, Helen E

AU - Lamb, Alastair D

AU - MacArthur, Stewart

AU - Stark, Rory

AU - Warren, Anne Y

AU - Mills, Ian G

AU - Neal, David E

PY - 2013/1/14

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N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Cell Line, Tumor

KW - Gene Expression Regulation, Neoplastic

KW - Histones

KW - Humans

KW - Male

KW - Mice

KW - Prostatic Neoplasms

KW - Receptors, Androgen

U2 - 10.1016/j.ccr.2012.11.010

DO - 10.1016/j.ccr.2012.11.010

M3 - Article

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SN - 1535-6108

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SP - 35

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JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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Cite this