Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice

Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in ba sal epithelial cells of prostate have been characterized. Transgene express ion led to activation of the IGF-1 receptor and spontaneous tumorigenesis i n prostate epithelium, Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small c ell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice greater than or eq ual to 6 months of age (38 mice total) was 50%, The development of neoplasi a in these transgenic mice appeared to follow a stepwise progression throug h early preneoplastic changes that ultimately culminated in frank neoplasia . These mice offer an animal model for prostate cancer that will allow stud y of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.