Cancer Cell
Volume 23, Issue 1, 14 January 2013, Pages 35-47
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Article
The Androgen Receptor Induces a Distinct Transcriptional Program in Castration-Resistant Prostate Cancer in Man

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Summary

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.

Highlights

► AR ChIP-seq in primary clinical material reveals persistent AR signaling in CRPC ► A tissue-specific transcriptional network exists in human prostate tissue ► AR signaling in CRPC is maintained via a distinct set of AR targets ► A core 16 gene set derived from this data is clinically relevant

Cited by (0)

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These authors contributed equally to this work

9

Present address: Prostate Cancer Research Group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, 0316 Oslo, Norway

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Present address: Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK