Prostate cancer is the second leading cause of cancer deaths in American males. Yet, the study of its genesis and progression has lagged behind that of other human neoplasias. Compounding this dilemma is a relatively meager understanding of the normal developmental processes that ultimately lead to the differentiation and architecture of the human prostate gland. As such, few insights into the etiology and cell of origin of prostate cancer have been forthcoming. Moreover, the intercellular signals and genes that mediate prostatic epithelium growth and differentiation are poorly understood. To begin to rectify these deficiencies in our knowledge of basic and essential processes in the human prostate we propose to generate and study a panel of conditionally-immortalized prostate cells derived from many of the cell types found in the normal human prostate gland. The following specific aims will be addressed by this proposal: 1. To generate a novel panel of conditionally-immortalized fetal, neonatal, and adult prostate cell lines via retrovirus-mediated gene transfer. 2. To generate a panel of differentiation-specific monoclonal antibodies recognizing prostate cell-surface antigens and characterize these antibodies as potential therapeutic and diagnostic reagents. 3. To identify soluble growth factors recovered from primary tissues that support and enhance the growth of prostate cells under non-permissive conditions for immortalization. 4. To clone cDNAs specifically expressed in senescent or terminally- differentiated prostate cells and characterize their molecular and biochemical properties.
