A Transgenic Rat Model of Prostate Carcinogenesis.

Abstract

We have generated a transgenic rat with the SV40 T antigen under probasin promoter control, allowing prostate specific gene expression. Males demonstrate atypical epithelial cell proliferation in the prostate from 4 weeks of age and develop prostate carcinomas at 100% incidence before they are 15 weeks old. These prostate caricnomas are completely androgen-dependent. Adequate materials of the prostate carcinomas, taking advantage of the rat transgenic model, allow us gene expression analysis for prostate carcinogenesis and involution process after castration. Male transgenic rats with a Sprague-Dawley genetic background were mated with wild-type females of F344, Wistar and ACI strains. F1 male transgenic hybrids with female Wistar and ACI rats had significantly lowered incidences of prostate carcinomas. However, the serum level of testosterone, and expression of the transgene, probasin, and the androgen receptor did not correlate with the strain variation in tumor development. These results clearly show that the transgenic rat is a good model for investigate prostate carcinogenesis and its modifying factors.