title: Hepatocyte nuclear factor-3 alpha (HNF-3alpha) negatively regulates androgen receptor transactivation in prostate cancer cells.
abstract: 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.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Puk-ku, Gwangju 500-757, Republic of Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Miok
authors.initials: M
authors.lastname: Hwang
authors.forename: Soma
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Hueng-Sik
authors.initials: HS
authors.lastname: Choi
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D011944:Receptors, Androgen