Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells
Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells
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DOI：
10.3177/jnsv.53.556
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发表时间：
2007-12-01
影响因子：
1.6
通讯作者：
Nakano, Yoshihisa
中科院分区：
文献类型：
--
作者：
Harada, Naoki;Murata, Yohei;Nakano, Yoshihisa
雄激素受体（AR）作为前列腺癌发生和进展的转录因子。已知白藜芦醇可抑制 AR 的功能并在转录水平上抑制 AR 的表达。本研究重点研究白藜芦醇对 AR 功能和翻译后 AR 水平的影响。在人前列腺癌 PC-3 细胞中，白藜芦醇以浓度依赖性方式抑制缺乏配体结合结构域的突变 AR（AR 的组成活性形式）和野生型 AR 的转录活性，表明白藜芦醇不会通过与 AR 的配体结合结构域结合来抑制 AR 的转录活性。此外，在白藜芦醇处理的 AR 阳性前列腺癌 LNCaP 细胞中，AR 蛋白的半衰期约为 4 小时。通过放线菌酮追踪测定，对照细胞中的时间约为 13 小时。这些结果表明白藜芦醇通过翻译后机制下调AR蛋白，并表明白藜芦醇对AR功能的抑制作用部分归因于翻译后AR水平的降低。
Androgen receptor (AR) functions as a transcriptional factor for the development and progression of prostate cancer. Resveratrol is known to inhibit the function of AR and to repress AR expression at the transcriptional level. This study focuses on the effects of resveratrol on the AR function and the post-translational AR level. Resveratrol repressed the transcriptional activities of a mutant AR lacking the ligand-binding domain, a constitutive active form of AR, and wild-type AR in a concentration-dependent manner in human prostate cancer PC-3 cells, indicating that resveratrol does not inhibit the transcriptional activity of AR through binding to the ligand-binding domain of AR. Furthermore, the half-life of AR protein was approximately 4 h in resveratrol-treated AR-positive prostate cancer LNCaP cells. compared to approximately 13 h in control cells, as determined by cycloheximide chase. These results indicate that resveratrol down-regulates AR protein through a post-translational mechanism and suggest that the inhibitory effect of resveratrol on AR function is partly attributable to a decrease in the post-translational AR level.