To: Flagrante Delictu who wrote (22633 ) 6/24/1998 8:26:00 AM From: Henry Niman Respond to of 32384
Here's the abstract describing anti-androgen stimulation of prostate cells: Vol. 95, Issue 13, 7379-7384, June 23, 1998 Biochemistry Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells Hiroshi Miyamoto*, Shuyuan Yeh*, George Wilding<Picture: dagger >, and Chawnshang Chang*,<Picture: dagger >,<Picture: Dagger > *ÿGeorge Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Biochemistry, University of Rochester Medical Center, Rochester, NY 14642; and <Picture: dagger >ÿUniversity of Wisconsin Comprehensive Cancer Center, Madison, WI 53792 Communicated by Jack Gorski, University of Wisconsin-Madison, Madison, WI, April 15,ÿ1998 (received for review January 9,ÿ1998) Although hormone therapy with antiandrogens has been widely used for the treatment of prostate cancer, some antiandrogens may act as androgen receptor (AR) agonists that may result in antiandrogen withdrawal syndrome. The molecular mechanism of this agonist response, however, remains unclear. Using mammalian two-hybrid assay, we report that antiandrogens, hydroxyflutamide, bicalutamide (casodex), cyproterone acetate, and RU58841, and other compounds such as genistein and RU486, can promote the interaction between AR and its coactivator, ARA70, in a dose-dependent manner. The chloramphenicol acetyltransferase assay further demonstrates that these antiandrogens and related compounds significantly enhance the AR transcriptional activity by cotransfection of AR and ARA70 in a 1:3 ratio into human prostate cancer DU145 cells. Our results suggest that the agonist activity of antiandrogens might occur with the proper interaction of AR and ARA70 in DU145 cells. These findings may provide a good model to develop better antiandrogens without agonist activity. ------------------------------------------------------------------------ <Picture: Dagger >ÿÿ To whom reprint requests should be addressed at: University of Rochester Medical Center, 601ÿElmwood Avenue, Box 626,ÿRochester, NY 14642.ÿe-mail: chang@pathology.rochester.edu.