INDUCTION OF MAMMARY-GLAND HYPERPLASIA AND CARCINOMAS IN TRANSGENIC MICE EXPRESSING HUMAN CYCLIN-E

Deregulated expression of several cell cycle regulatory genes has been demonstrated to be associated with cancer. In particular, a strong co rrelation has been established between inappropriate cyclin E expressi on and human breast cancer. To determine the ability of cyclin E to pl ay a causative role in mammary tumorigenesis, regulatory sequences fro m the ovine beta-lactoglobulin gene were utilized to specifically targ et expression of human cyclin E to the mammary glands of pregnant and lactating mice. Lactating mammary glands of transgenic mice expressing cyclin E contained areas of hyperplasia, primarily papillary projecti ons of hyperplastic cells, which were rarely observed in lactating gla nds of control mice. Over 10% of female cyclin E transgenic mice have developed mammary carcinomas, with latencies ranging from 8 to 13 mont hs. Tumor analysis revealed the presence of transgene-specific cyclin E RNA and protein, as well as cyclin E- and cdk2-associated kinase act ivity, suggesting that cyclin E is likely a contributing component of tumorigenic progression in this model system.