ELF5 介导的 AR 激活调控前列腺癌进展。
ELF5-Mediated AR Activation Regulates Prostate Cancer Progression.
机构信息
Department of Urology, Tianjin Institute of Urology, Tianjin Medical University Second Hospital, Tianjin 300211, China.
Department of Urology, Tianjin Third Central Hospital, Tianjin 300170, China.
出版信息
Sci Rep. 2017 Mar 13;7:42759. doi: 10.1038/srep42759.
The transcription factor E74-like factor 5 (ELF5) is a potent antioncogene that can prevent epithelial-mesenchymal transition (EMT) and metastasis in prostate cancer (PCa). However, little is known how it suppress the tumor growth and if it can interact with androgen receptor (AR). In this study, we find that the ELF5 is frequently expressed in AR activated PCa cells, where it binds to AR acting as a physiological partner and negatively regulates its transcriptional activity. In addition, the interaction between ELF5 and AR is androgen-dependent. Downregulation of ELF5 by shRNA increases the expression of AR-response genes and the progression of PCa. Moreover, ELF5 is a AR-dependent gene that its expression can be induced by androgen and suppressed by antiandrogen treatment. Notably, forced reduction of ELF5 in LNCaP cells facilitates the binding of AR to ARE in ELF5 gene and enabling its transcription, so that low level ELF5 can turn up its own expression by the negative feedback loop.
转录因子 E74 样因子 5（ELF5）是一种有效的抑癌基因，可预防前列腺癌（PCa）中的上皮-间充质转化（EMT）和转移。然而，人们对其如何抑制肿瘤生长以及是否可以与雄激素受体（AR）相互作用知之甚少。在这项研究中，我们发现 ELF5 在 AR 激活的 PCa 细胞中频繁表达，在这些细胞中，ELF5 作为生理伴侣与 AR 结合，从而负调控其转录活性。此外，ELF5 与 AR 之间的相互作用依赖于雄激素。shRNA 下调 ELF5 会增加 AR 反应基因的表达并促进 PCa 的进展。此外，ELF5 是一个 AR 依赖性基因，其表达可被雄激素诱导，抗雄激素治疗可抑制其表达。值得注意的是，在 LNCaP 细胞中强制降低 ELF5 的水平可促进 AR 与 ELF5 基因中的 ARE 结合并使其转录，从而使低水平的 ELF5 能够通过负反馈回路上调自身表达。
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