ABSTRACT

Signal transduction regulation was interrupted in four independent transgenic mice by expressing the polyomavirus middle T (PyMT) gene, to affect the growth and development of the prostate gland and other urogenital tissues. Expression of PyMT was directed to these tissues by a novel, androgen-inducible expression vector based on the rat C3(1) gene. Epithelial growth disturbances ranging from tissue hyperplasia, cellular dysplasia to invasive carcinoma were observed in the ventral and dorsal prostate. Similar abnormalities were seen in the coagulating gland, epididymis, and vas deferens. The abnormalities were recognized by histological changes within the ventral and dorsal prostates were recognized by histologic disorganization, nuclear pleomorphism, increased mitosis and abnormal ploidy. Transgene transcription was detected in all affected tissues, demonstrating that the C3(1)-based vector targeted androgen sensitive urogenital tissues, especially the prostate. Therefore, the expression of a protein altering signal transduction pathways disrupts urogenital growth and development.