title: Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E.
abstract: 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.
authors.affiliation: Department of Cellular Sciences, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA. bortner-dm@glaxo.com
authors.forename: D M
authors.initials: DM
authors.lastname: Bortner
authors.forename: M P
authors.initials: MP
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D042846:CDC2-CDC28 Kinases; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia / Q000235:genetics*; D007774:Lactation; D007782:Lactoglobulins / Q000235:genetics; D008223:Lymphoma / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012756:Sheep
chemical_list: D016213:Cyclins; D007782:Lactoglobulins; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases