A previous human trial with selenized yeast showed that selenium supplementation significantly reduced the incidence of lung, colon, and prostate cancers. Based on these encouraging results, the National Cancer Institute (NCI) launched the prostate cancer Selenium and Vitamin E Chemoprevention Trial (SELECT) in the fall of 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 the SELECT by conducting mechanism-based research on key molecular targets that might be responsible for initiating the signaling cascades that ultimately lead to selenium-mediated growth arrest of the cancer cells. The gene that we are focusing on in this proposal, GKLF, encodes a protein involved in gene expression control. GKLF is a potential tumor suppressor gene and has a well-documented role in regulating cell growth. The expression level and activity of GKLF are markedly increased by selenium treatment in prostate cancer cells, and the induction occurs early and persists following selenium exposure. As an immediate target, GKLF could modulate the expression of a wide spectrum of genes and thus serve as a key trigger of selenium action. A major goal of this proposal is to study the role of GKLF in contributing to the molecular effects of selenium in cancer chemoprevention. The results obtained from this study could lay the groundwork for developing a custom-tailored intervention strategy in selecting high-risk prostate cancer patients for selenium intervention according to their genetic "fingerprints."