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Mol. Cell. Biol., Jan 1997, 453-459, Vol 17, No. 1
Copyright © 1997, American Society for Microbiology

Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E

DM Bortner and MP Rosenberg
Department of Cellular Sciences, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA. bortner- dm@glaxo.com

Deregulated expression of several cell cycle regulatory genes has been demonstrated to be associated with cancer. In particular, a strong correlation has been established between inappropriate cyclin E expression and human breast cancer. To determine the ability of cyclin E to play a causative role in mammary tumorigenesis, regulatory sequences from the ovine beta-lactoglobulin gene were utilized to specifically target 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 projections of hyperplastic cells, which were rarely observed in lactating glands of control mice. Over 10% of female cyclin E transgenic mice have developed mammary carcinomas, with latencies ranging from 8 to 13 months. Tumor analysis revealed the presence of transgene-specific cyclin E RNA and protein, as well as cyclin E- and cdk2-associated kinase activity, suggesting that cyclin E is likely a contributing component of tumorigenic progression in this model system.


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