CHARACTERIZATION OF PROSTATIC EPITHELIAL-CELL LINES DERIVED FROM TRANSGENIC ADENOCARCINOMA OF THE MOUSE PROSTATE (TRAMP) MODEL

To develop a syngeneic transplantable system to study immunotherapeuti c approaches for the treatment of prostate cancer, three cell lines we re established from a heterogeneous 32 week tumor of the transgenic ad enocarcinoma mouse prostate (TRAMP) model, TRAMP is a transgenic line of C57BL/6 mice harboring a construct comprised of the minimal -426/+2 8 rat probasin promoter driving prostate-specific epithelial expressio n of the SV40 large T antigen, TRAMP males develop histological prosta tic intraepithelial neoplasia by 8-12 weeks of age that progress to ad enocarcinoma with distant metastases by 24-30 weeks of age. The three cell lines (TRAMP-C1, TRAMP-C2, and TRAMP-C3) express cytokeratin, E-c adherin, and androgen receptor by immunohistochemical analysis and do not appear to have a mutated p53. Although TRAMP-C1 and TRAMP-C2 are t umorigenic when grafted into syngeneic C57BL/6 hosts, TRAMP-C3 grows r eadily in vitro but does not form tumors, The T antigen oncoprotein is not expressed by the cell lines in vitro or in vivo. The rationale fo r establishing multiple cell lines was to isolate cells representing v arious stages of cellular transformation and progression to androgen-i ndependent metastatic disease that could be manipulated in vitro and, in combination with the TRAMP model, provide a system to investigate t herapeutic interventions, such as immunotherapy prior to clinical tria ls.