Neoplastic transformation of prostatic and urogenital epithelium by the polyoma virus middle T gene

Male transgenic mice expressing the polyomavirus middle T (PyV-MT) gene exhibited growth and developmental abnormalities in prostatic and other urogenital epithelium. Expression of PyV-MT was directed to these tissues by a novel, androgen-inducible expression vector based on the rat C3(1) gene. Epithelial growth disturbances (hyperplasia, dysplasia, and invasive carcinoma) were observed in the ventral and dorsal prostate, coagulating gland, epididymis, and vas deferens. The abnormalities were characterized by histological disorganization, nuclear pleomorphism, increased mitoses, and abnormal DNA content. Transgene transcription was detected in affected tissues, indicating that the C3(1)-based vector targeted androgen-sensitive urogenital tissues, especially the prostate. These results demonstrated that expression of a gene, the protein of which is known to interact with cellular proteins involved in signal transduction, dramatically disrupted urogenital growth and development.