History Features TRAMP and the Neuroendocrine Phenotype Uses TRAMP HistoPathology- self guided slide show Video Instruction Manual and Guide A transgene carrying the -426/+28 fragment of the rat probasin (PB) gene fused to the SV40 T antigen (Tag) has been used to generate an independent transgenic autochthonous model for prostate cancer in the C57Bl/6 inbred strain of mice. Expression of the PB-Tag transgene is initially regulated by androgens and restricted to the prostate epithelial cells of the dorsolateral and ventral lobes. By the time the mice are 12 weeks of age, TRAMP mice histologically display mild to severe hyperplasia with cribriform structures. Severe hyperplasia and adenocarcinoma is observed by 18 weeks of age. By 24-30 weeks of age, all TRAMP males display primary tumors and metastasis are commonly detected in the lymph nodes and lungs and less frequently in the bone, kidney and adrenal glands. The epithelial origin of the tumors and metastatic deposits has been demonstrated. When castrated at 12 weeks of age, 80% of TRAMP mice ultimately develop prostate cancer, demonstrating that the tumors are at least initially androgen dependent. Interestingly, the castrated mice develop more poorly differentiated primary tumors and twice the incidence of metastatic disease compared to non-castrate TRAMP controls. The TRAMP mice have also been used as a source for the development of new research materials and at least three novel prostate cancerepithelial cell lines (TRAMP-C1, -C2 and -C3) have been established from the primary prostate tumors. These cell lines all express the androgen receptor but no longer express the SV40 early genes. TRAMP-C1 and -C2 form tumors when grafted subcutaneously into syngeneic C57Bl/6 hosts.