A previous human trial with selenized yeast showed that selenium supplementation significantly reduced the incidence of lung, colon, and prostate cancers. The results were so encouraging that the National Cancer Institute is sponsoring the prostate cancer Selenium and Vitamin E Chemoprevention Trial (SELECT) scheduled to begin in 2001. One of the secondary objectives of this trial is to study cellular and molecular biomarkers and to delineate their relevance with respect to prostate carcinogenesis and drug effects. Our long term goal is to provide supportive information to SELECT by doing research on molecular biomarkers that are associated with the mechanism of action of selenium in prostate cancer prevention. We plan to use both androgen-responsive and -unresponsive human prostate cancer cells to investigate the molecular effects of selenium, with special emphasis on cell signaling pathways associated with cell growth inhibition and induction of apoptosis. Some of these signaling molecules could conceivably be used as biomarkers to guide the selection of prostate cancer patients who are likely to benefit from selenium supplementation for prevention of disease recurrence. A state-of-the-art cDNA array technology will be used to speed up the identification of sensitive and reliable biomarkers. This approach can ultimately be applied to implement a custom-tailored intervention strategy for high risk prostate cancer patients.