Prostate and breast cancer are major causes of morbidity and mortality in the U.S. and their incidence appears to be rising. Although several animal models for breast cancer have been developed, few useful animal models of prostate cancer exist. Transgenic animal models of human disease are important systems for helping to elucidate mechanisms of oncogenesis in vivo. Transgenic models allow for the targeting or overexpression of various types of genes including oncogenes, growth factors and receptors to particular tissues to study the biologic consequences in a naturally developing animal system. The initial goals of this project have been realized which include 1) the development of a transgenic mouse model for the multistage development of prostate cancer; and 2) the identification of genetic regulatory elements which can be utilized to target the expression of various genes to the prostatic epithelium. The expression of the early region of SV40 (Tag) has been successfully targeted to the mouse prostate through those of the 5' regulatory region of the hormone responsive rat C3(1) gene. Two transgenic founder lines have been propagated in which male animals develop prostate hyperplasia early in life which progresses to overt adenocarcinoma over several months. Interestingly, female animals from the same lines develop hyperplasia of the mammary glands which progresses to adenocarcinoma by six months of age. In addition to these abnormalities, these transgenic mice develop other unusual phenotypic changes including generalized chondrodysplasia, heterotopic bone formation, and occasional appearance of osteosarcomas and thyroid carcinoma.
