| 摘要 |
Disclosed are transgenic mice that produces prostate tumors and faithfully recapitulate many of the features of human prostatic carcinoma. It has been discovered that transcriptional regulatory elements active in Paneth cells, granule goblet cells, intermediate cells, or a combination, when used to express Simian Virus 40 large T antigen (TAg) in a transgenic mouse leads to development of prostate tumors in the mouse. The transcriptional regulatory elements are derived from the cryptdin-2 (CR2) gene. The disclosed mice develop prostatic intraepithelial neoplasia (PIN) at an early age. Progression with local invasion, loss of androgen-dependence and eventual metastases are hallmarks of the disclosed transgenic mice. Preferred embodiments of the disclosed transgenic mice have several important characteristics: (1) the disease is fully penetrant-all mice containing the SV40 TAg transgene develop prostatic cancer; (2) the first appearance of SV40 TAg always coincides with the appearance of cellular atypia in prostatic acini; (3) the rate of progression of the neoplasia is rapid; (4) prostatic adenocarcinomas in the transgenic mice exhibit foci of neuroendocrine differentiation; (5) metastatic lesions are common in the lymph nodes, liver, lung, and bone of the disclosed transgenic mice and are evident early in life; and (6) the lifespan of the disclosed transgenic animals is not shortened by transgene-related pathology in other organs-female transgenic mice develop normally and have a normal lifespan.
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