Hepatocyte nuclear factor-3 alpha (HNF-3alpha) negatively regulates androgen receptor transactivation in prostate cancer cells.
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.
Lee
Hyun Joo
HJ
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Puk-ku, Gwangju 500-757, Republic of Korea.
Hwang
Miok
M
Chattopadhyay
Soma
S
Choi
Hueng-Sik
HS
Lee
Keesook
K
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
C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D011944:Receptors, Androgen