Metastatic prostate cancer in a transgenic mouse.

TLDR

The TRAMP transgenic mouse model, derived from PB‑Tag line 8247, has been established for studying prostate cancer. This study aims to map the temporal and spatial progression of transgene expression and to characterize metastatic disease in the TRAMP model. The TRAMP model supplies a reliable source of primary and metastatic tumors for histopathobiological and molecular analyses to elucidate early events in prostate cancer genesis, progression, and metastasis. TRAMP mice express the T‑antigen by 8 weeks, develop dorsolateral prostate pathology by 10 weeks, and exhibit distant metastases—primarily to periaortic lymph nodes and lungs, occasionally to kidney, adrenal gland, and bone—by 12 weeks, with 100 % metastatic burden in lymph nodes or lungs by 28 weeks, accompanied by loss of E‑cadherin expression as tumors dedifferentiate.

Abstract

We have previously reported the development of a transgenic mouse model for prostate cancer derived from PB-Tag transgenic line 8247, henceforth designated the TRAMP (transgenic adenocarcinoma mouse prostate) model. We now describe the temporal and spatial consequences of transgene expression and report the identification and characterization of metastatic disease in the TRAMP model. TRAMP mice characteristically express the T antigen oncoprotein by 8 weeks of age and develop distinct pathology in the epithelium of the dorsolateral prostate by 10 weeks of age. Distant site metastases can be detected as early as 12 weeks of age. The common sites of metastases are the periaortic lymph nodes and lungs, with occasional metastases to the kidney, adrenal gland, and bone. By 28 weeks of age, 100% harbor metastatic prostate cancer in the 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 provides a consistent source of primary and metastatic tumors for histopathobiological and molecular analysis to further define the earliest molecular events involved in the genesis, progression, and metastasis of prostate cancer.