화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.367, No.2, 481-486, 2008
Hepatocyte nuclear factor-3 alpha (HNF-3 alpha) 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-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.