Lee Hyun Joo, Hwang Miok, Chattopadhyay Soma, Choi Hueng-Sik, Lee Keesook
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Puk-ku, Gwangju 500-757, Republic of Korea.
Biochem Biophys Res Commun. 2008 Mar 7;367(2):481-6. doi: 10.1016/j.bbrc.2007.12.162. Epub 2008 Jan 4.
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-3alpha (HNF-3alpha) 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-3alpha functions as a novel corepressor of AR in prostatic cells. HNF-3alpha represses AR transactivation on target promoters containing the androgen response element (ARE) in a dose-dependent manner. HNF-3alpha interacts physically with AR, and negatively regulates AR transactivation via competition with AR coactivators, including GRIP1. Furthermore, HNF-3alpha overexpression reduces the androgen-induced expression of prostate-specific antigen (PSA) in LNCaP cells. Taken together, our findings indicate that HNF-3alpha is a novel corepressor of AR, and predict its effects on the proliferation of prostate cancer cells.
雄激素受体（AR）参与前列腺癌的发生和发展。然而，其发生机制仍未完全明确。在以往的报道中，肝细胞核因子-3α（HNF-3α）已被证实在前列腺上皮中表达，并被确定可调节前列腺特异性基因的转录。在本研究中，我们报道HNF-3α在前列腺细胞中作为AR的一种新型共抑制因子发挥作用。HNF-3α以剂量依赖的方式抑制含有雄激素反应元件（ARE）的靶启动子上的AR反式激活。HNF-3α与AR发生物理相互作用，并通过与包括GRIP1在内的AR共激活因子竞争来负向调节AR反式激活。此外，HNF-3α的过表达降低了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-3α是AR的一种新型共抑制因子，并预示了其对前列腺癌细胞增殖的影响。
