ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer
ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer
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DOI：
10.1016/j.ccell.2019.01.008
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发表时间：
2019-03-18
期刊：
影响因子：
50.3
通讯作者：
Brown, Myles
中科院分区：
文献类型：
--
作者：
Cato, Laura;de Tribolet-Hardy, Jonas;Brown, Myles
前列腺癌（PCa）的雄激素剥夺疗法对早期疾病患者有益，但随着PCa进展到去势抵抗状态（CRPC），雄激素剥夺疗法变得无效。最初，CRPC仍然依赖于雄激素受体（AR）信号传导，通常通过全长AR（ARfl）的表达增加或显性活性剪接变体如ARv7的表达。我们在ARv7依赖性CRPC模型中显示，ARv7与ARfl结合在一起以抑制一组生长抑制基因的转录。ARv7抑制靶点的表达和ARv7蛋白表达呈负相关，并可预测PCa患者的预后。我们的研究结果为ARv7在CRPC中的作用提供了见解，并为依赖ARv7的肿瘤定义了一组潜在的生物标志物。
Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, often through increased expression of full-length AR (ARfl) or expression of dominantly active splice variants such as ARv7. We show in ARv7-dependent CRPC models that ARv7 binds together with ARfl to repress transcription of a set of growth-suppressive genes. Expression of the ARv7-repressed targets and ARv7 protein expression are negatively correlated and predicts for outcome in PCa patients. Our results provide insights into the role of ARv7 in CRPC and define a set of potential biomarkers for tumors dependent on ARv7.