The Androgen Receptor Induces a Distinct Transcriptional Program in Castration-Resistant Prostate Cancer in Man
The Androgen Receptor Induces a Distinct Transcriptional Program in Castration-Resistant Prostate Cancer in Man
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DOI：
10.1016/j.ccr.2012.11.010
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发表时间：
2013-01-14
期刊：
影响因子：
50.3
通讯作者：
Neal, David E.
中科院分区：
文献类型：
--
作者：
Sharma, Naomi L.;Massie, Charlie E.;Neal, David E.
雄激素受体（AR）调节男性前列腺细胞的生长，前列腺癌是英国男性最常见的癌症。我们对人类前列腺癌组织（包括去势抵抗性前列腺癌（CRPC））中的 AR 结合位点进行了全面分析。我们在 CRPC 组织中发现了数千个 AR 结合位点，其中大多数在 PC 细胞系中未发现。许多邻近基因在异种移植物中显示出 AR 调节，但在培养的 LNCaP 中则不然，这表明一组体内限制的 AR 调节基因。功能研究支持了指导 AR 结合的体内信号传导改变的模型。我们在临床数据集中发现了一个 16 基因特征，其性能优于更大的体外衍生特征，显示了持续 AR 信号传导在 CRPC 中的重要性。
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.