METASTATIC PROSTATE-CANCER IN A TRANSGENIC MOUSE

We have previously reported the development of a transgenic mouse mode l for prostate cancer derived from PB-Tag transgenic line 8247, hencef orth designated the TRAMP (transgenic adenocarcinoma mouse prostate) m odel. We now describe the temporal and spatial consequences of transge ne expression and report the identification and characterization of me tastatic disease in the TRAMP model, TRAMP mice characteristically exp ress the T antigen oncoprotein by 8 weeks of age and develop distinct pathology in the epithelium of the dorsolateral prostate by 10 weeks o f age, Distant site metastases can be detected as early as 12 weeks of ape. The common sites of metastases are the periaortic lymph nodes an d lungs, with occasional metastases to the kidney, adrenal gland, and bone, By 28 weeks of age, 100% harbor metastatic prostate cancer in th e lymph nodes or lungs. We have also demonstrated the loss of normal E -cadherin expression, as observed in human prostate cancer, as primary tumors become less differentiated and metastasize, The TRAMP model pr ovides a consistent source of primary and metastatic tumors for histop athobiological and molecular analysis to further define the earliest m olecular events involved in the genesis, progression, and metastasis o f prostate cancer.