Characterization of the autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) as a model to study effects of castration therapy.

Abstract

BACKGROUND: In order to learn more about short- and long-term effects of castration therapy, relevant model systems for prostate cancer are required. In this study, we examined whether the transgenic adenocarcinoma of the mouse prostate (TRAMP) tumor response to castration in C57BL/6 mice mimics that seen in patients. METHODS: Transgenic animals were examined before and 3 days after castration, at the ages of 17, 24, and 36 weeks. Moreover, 24-weeks old animals were castrated and followed for 6 months. Immunohistochemistry (IHC) and stereology were used to evaluate epithelial cell proliferation and death, blood vessel volume, androgen receptor (AR) expression, and transgenic expression of SV40 large T. RESULTS: Cancer developed preferentially in the dorso-lateral prostate lobe. Tumor burden and incidence of metastases increased with age. The majority of tumors were well differentiated, while poorly differentiated, large tumors and macroscopic metastases developed in 8% of the animals. Well and moderately differentiated tumors responded to castration with cessation of proliferation and induction of apoptosis. Poorly differentiated tumors and metastases did not respond. Castration prevented local tumor growth for at least 6 months in 82% of the cases. Although, 45% of the treated animals developed wide-spread metastatic disease suggesting that castration may enhance growth of distant metastases. CONCLUSIONS: The C57Bl/6 TRAMP tumor in several ways mimics how prostate cancer in patients responds to castration both in the short and long term, but some differences may also exist. This model can preferably be used to elucidate how this treatment works, and to test how it can be improved by additional therapies.