Hepatocyte nuclear factor-3 alpha (HNF-3alpha) negatively regulates androgen receptor transactivation in prostate cancer cells

Biochemical and Biophysical Research Communications
Hyun Joo LeeKeesook Lee

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.

References

Feb 1, 1989·Cancer Genetics and Cytogenetics·A R BrothmanD J Merchant
Dec 15, 1995·The Journal of Biological Chemistry·E LangleyE M Wilson
Dec 1, 1996·The Journal of Clinical Endocrinology and Metabolism·B JinD J Handelsman
Dec 19, 1996·Nature·A J Bannister, T Kouzarides
Jan 5, 2000·Seminars in Surgical Oncology·L J Denis, K Griffiths
Jan 12, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yongjun TanRobert H Costa
Jan 31, 2002·Molecular Endocrinology·Zhong-xun ZhouFrank S French
Apr 12, 2002·Endocrine Reviews·Cynthia A Heinlein, Chawnshang Chang
Jun 5, 2002·Nature Reviews. Cancer·Samuel R Denmeade, John T Isaacs
Sep 26, 2002·Developmental Biology·Peter Carlsson, Margit Mahlapuu
Oct 3, 2003·Cancer Cell·Katharine Ellwood-YenCharles L Sawyers
Nov 13, 2003·Molecular and Cellular Biology·Maofu FuRichard G Pestell
Apr 15, 2004·Endocrine Reviews·Cynthia A Heinlein, Chawnshang Chang
Sep 16, 2004·Journal of Cellular Biochemistry·Joshua Kim, Gerhard A Coetzee
Sep 25, 2004·The Prostate·Janni MirosevichRobert J Matusik
Sep 25, 2004·The Prostate·Hiroshi MiyamotoChawnshang Chang
Mar 8, 2005·Experimental Cell Research·Per-Henrik HolmqvistOrjan Wrange

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Citations

Apr 3, 2013·European Journal of Pharmacology·Marjolein DroogWilbert Zwart
Jul 17, 2012·The Journal of Biological Chemistry·Chin-Hee SongKeesook Lee
Nov 26, 2011·Bioscience Reports·Gina M Bernardo, Ruth A Keri
Apr 28, 2009·Genes, Chromosomes & Cancer·Brian J HensonSusanne M Gollin
Mar 16, 2011·Histopathology·Rohit K JainSunil S Badve
Mar 12, 2009·Current Opinion in Lipidology
Apr 25, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity

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