REGULATION OF ANDROGEN RECEPTOR ACTIVITY

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The major objectives of this proposal are to obtain training and experience in molecular biology techniques so that they can be used in the Principal Investigator's laboratory in his research. The training will be provided by Drs. Frank French and Elizabeth Wilson at the University of North Carolina at Chapel Hill. The designated trainee will be Jaime Steinsapir, M.D., Ph.D. who will work for at least one year after completion of training in the P.I.'s laboratory. The research to be conducted is as follows: Prostate cells are responsive to androgens by virtue of the presence of functional androgen receptors (AR). The goal of these studies is to determine mechanisms by which androgens and antiandrogens control AR activity and turnover in normal and neoplastic prostate cells. The effects of androgen withdrawal on androgen and antiandrogen control of mRNA-AR levels and initial transcription rate of the AR gene will be examined in rat ventral prostate and human prostate cancer cells (LNCaP). The assessment of the effects of androgen and antiandrogens on the transcriptional activity of the AR gene upstream enhancer/promoter coupled with studies on AR binding to promoter sequences should determine specific response elements involved in AR autoregulation of the AR gene. The results will further help to understand the molecular mechanisms of regulation of AR gene transcription by androgens and antiandrogens. This project will be used as a basis for training in the use of molecular biology techniques in hormone receptor synthesis and turnover.