Prostate cancer is the second cause of cancer death in the male population. The lack of progress in treatment and management of this disease is hampered by inadequate experimental animal models. The purpose of this project is to develop and establish an efficient and reproducible animal model system for inducing prostate carcinogenesis; analyze the molecular and cellular events following the development of prostate cancer and to identify agents that prevent and/or suppress prostate cancer incidence. We have initiated induction of prostate carcinogenesis by initiation with N-methyl-nitrosourea (NMU) and promotion with testosterone propionate (TP) in Lobund/Wistar rats of varying age ranging from 2-4 months old. We have partially succeeded in growing primary cultures of normal rat prostate epithelium for 3 weeks in chemically defined media supplemented with exogenous nutrients and growth promoting substances. Using 3 month old rats, we have shown increased levels of TGF-beta1 and beta3 message and protein at 3-6 days following castration. This effect was reversed by treatment with TP. In collaboration with Dr. Morris Pollard, Lobund Laboratory, we have demonstrated for the first time decreased incidence of prostate cancer in MNU/TP treated animals fed with N- (4-Hydroxyphenyl) retinamide.
