Gene profiling of genistein’s effect in men with prostate cancer.

5265 Genistein is a putative prostate cancer (PCa) chemopreventative agent. Both epidemiological studies conducted by others, as well as preclinical molecular pharmacology studies performed by us, indicate that genistein has the potential to inhibit metastasis. Prospective studies aimed at evaluating the effects of genistein upon prostate cells in man are lacking. As genistein may be an effective chemopre ventive agent but may be operating through other mechanisms, it is also notable that effective methods to broadly screen for molecular effects in target tissue in man are also lacking. After completing a phase I trial, we have implemented a phase 2 trial in men about to undergo radical prostatectomy, thus providing tissue from those treated with genistein and controls. We have recently developed a robust and accurate method which allows high density gene array profiles to be performed on specific prostate cell populations recovered from intact tissue by laser capture microdissection. In the current study we examine normal prostate epithelial cells, and compare gene expression profiles between control subjects (N = 11) and genistein treated (N = 8). From over 12,000 genes analyzed, 10 were identified as significantly differentially expressed. Importantly, 3 genes have a clear mechanistic relationship to genistein. HCF2 is an anticoagulant factor involved in cell migration. BASP1 is a neural tissue-enriched protein and motility-associated factor. HSP90 is in the same family as HSP27, which we have recently shown regulates PCa cell matrix metalloproteinase type 2 (MMP-2) induction and invasion. In summary, robust in vivo molecular profiling at the level of individual cell types is now possible, and provides key mechanistic information about therapeutic intervention.