Prostate carcinomas developing in transgenic rats with SV40 T antigen expression under probasin promoter control are strictly androgen dependent

We have generated a transgenic rat with the SV40 T antigen under probasin p romoter control, allowing prostate-specific gene expression. Males demonstr ate atypical epithelial cell proliferation in the prostate from I weeks of age and develop prostate carcinomas at 100% incidence before they are 15 we eks old, Castration at 5 weeks of age was found to inhibit the prostate tum or formation completely, whereas testosterone propionate administration ind uced marked cell proliferation as well as microinvasion in prostate carcino mas. Castration at 20 weeks of age, after tumor development, even with test osterone propionate treatment, induced complete tumor involution within 5 w eeks. To investigate the underling processes, sequential histological chang es were monitored 1, 2, 3, 7, 14, and 21 days after castration. At days 1-3 , many apoptotic bodies and inflammatory cells, including foam cells, were observed, and clear glandular structures were no longer evident in the tumo rs. Seven days after castration, most glands were involved, and nuclei of t he cells did not show atypia, After 14 and 21 days, only atrophic glands we re observed. During this process, expression of caspase 3, caspase 6, BAX, bcl-x, TRPM-2, and MMP7 genes was apparently increased. Comparison of the g ene expression profile between a prostate carcinoma in a transgenic animal and a normal prostate of a wild-type rat by a cDNA array technique was also conducted. The results suggested that our model is suitable to investigate mechanisms of carcinogenesis, including androgen dependence, involution, a nd apoptosis.