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[Cancer Research 60, 5946-5949, November 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Breast Cancer Susceptibility Gene 1 (BRCA1) Is a Coactivator of the Androgen Receptor1

John J. Park2, Ryan A. Irvine2, Grant Buchanan, Stephen S. Koh, Jinha M. Park, Wayne D. Tilley, Michael R. Stallcup, Michael F. Press3 and Gerhard A. Coetzee3,4

Breast Cancer Research Program of the University of Southern California/Norris Comprehensive Cancer Center [J. J. P., M. F. P., G. A. C.], the Departments of Pathology [J. J. P., S. S. K., J. M. P., M. R. S., M. F. P.], Urology [R. A. I., G. A. C.], Molecular Microbiology and Immunology [R. A. I., G. A. C.], Biochemistry and Molecular Biology [M. R. S.], and Preventive Medicine [G. A. C.], Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9176, and Flinders Cancer Centre, Flinders University and Medical Centre, Adelaide, South Australia 5042 Australia [G. B., W. D. T.]

In the present study, the role of BRCA1 in ligand-dependent androgen receptor (AR) signaling was assessed. In transfected prostate and breast cancer cell lines, BRCA1 enhanced AR-dependent transactivation of a probasin-derived reporter gene. The effects of BRCA1 were mediated through the NH2-terminal activation function (AF-1) of the receptor. Cotransfection of p160 coactivators markedly potentiated BRCA1-mediated enhancement of AR signaling. In addition, BRCA1 was shown to interact physically with both the AR and the p160 coactivator, glucocorticoid receptor interacting protein 1. These findings suggest that BRCA1 may directly modulate AR signaling and, therefore, may have implications regarding the proliferation of normal and malignant androgen-regulated tissues.




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