Hepatocyte nuclear factor-3 alpha (HNF-3α) negatively regulates androgen receptor transactivation in prostate cancer cells
Hepatocyte nuclear factor-3 alpha (HNF-3α) negatively regulates androgen receptor transactivation in prostate cancer cells
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DOI：
10.1016/j.bbrc.2007.12.162
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发表时间：
2008-03-07
影响因子：
3.1
通讯作者：
Lee, Keesook
中科院分区：
文献类型：
--
作者：
Lee, Hyun Joo;Hwang, Miok;Lee, Keesook
雄激素受体（AR）参与前列腺癌的发生和发展。然而，发生这种情况的机制仍然不完全清楚。在先前的报道中，肝细胞核因子-3 α (HNF-3 α)已被证明在前列腺上皮中表达，并被确定调节前列腺特异性基因的转录。在这项研究中，我们报道了HNF-3 α在前列腺细胞中作为一种新的AR辅助抑制因子发挥作用。HNF-3 α以剂量依赖的方式抑制含有雄激素反应元件（ARE）的目标启动子上的AR交易激活。HNF-3a与AR发生物理相互作用，并通过与AR共激活因子（包括GRIP1）竞争，负向调节AR交易激活。此外，HNF-3 α过表达可降低LNCaP细胞中雄激素诱导的前列腺特异性抗原（PSA）的表达。综上所述，我们的研究结果表明，HNF-3 α是一种新的AR协同抑制因子，并预测其对前列腺癌细胞增殖的影响。(c) 2007爱思唯尔公司版权所有。
The androgen receptor (AR) is involved in the development and progression of prostate cancers. However, the mechanisms by which this occurs remain incompletely understood. In previous reports, hepatocyte nuclear factor-3 alpha (HNF-3 alpha) has been shown to be expressed in the epithelia of the prostate gland, and has been determined to regulate the transcription of prostate-specific genes. In this study, we report that HNF-3 alpha functions as a novel corepressor of AR in prostatic cells. HNF-3 alpha represses AR transactivation on target promoters containing the androgen response element (ARE) in a dose-dependent manner. HNF-3a interacts physically with AR, and negatively regulates AR transactivation via competition with AR coactivators, including GRIP1. Furthermore, HNF-3 alpha overexpression reduces the androgen-induced expression of prostate-specific antigen (PSA) in LNCaP cells. Taken together, our findings indicate that HNF-3 alpha is a novel corepressor of AR, and predict its effects on the proliferation of prostate cancer cells. (c) 2007 Elsevier Inc. All rights reserved.