PMID:15314168

Citation	Hulit, J, Wang, C, Li, Z, Albanese, C, Rao, M, Di Vizio, D, Shah, S, Byers, SW, Mahmood, R, Augenlicht, LH, Russell, R and Pestell, RG (2004) Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice. Mol. Cell. Biol. 24:7598-611
Abstract	Constitutive beta-catenin/Tcf activity, the primary transforming events in colorectal carcinoma, occurs through induction of the Wnt pathway or APC gene mutations that cause familial adenomatous polyposis. Mice carrying Apc mutations in their germ line (ApcMin) develop intestinal adenomas. Here, the crossing of ApcMin with cyclin D1-/- mice reduced the intestinal tumor number in animals genetically heterozygous or nullizygous for cyclin D1. Decreased tumor number in the duodenum, intestines, and colons of ApcMin/cyclin D1+/- mice correlated with reduced cellular proliferation and increased differentiation. Cyclin D1 deficiency reduced DNA synthesis and induced differentiation of colonic epithelial cells harboring mutant APC but not wild-type APC cells in vivo. In previous studies, the complete loss of cyclin D1 through homozygous genetic deletion conveyed breast tumor resistance. The protection of mice, genetically predisposed to intestinal tumorigenesis, through cyclin D1 heterozygosity suggests that modalities that reduce cyclin D1 abundance could provide chemoprotection.
Links	PubMed PMC507010 Online version:10.1128/MCB.24.17.7598-7611.2004
Keywords	Adenomatous Polyposis Coli Protein/genetics; Adenomatous Polyposis Coli Protein/metabolism; Animals; Cell Differentiation/physiology; Colon/anatomy & histology; Colon/metabolism; Colon/pathology; Cyclin D1/genetics; Cyclin D1/metabolism; Cytoskeletal Proteins/metabolism; Epithelial Cells/cytology; Epithelial Cells/physiology; Female; Gastrointestinal Neoplasms/metabolism; Gastrointestinal Neoplasms/pathology; Genetic Predisposition to Disease; Genotype; Humans; Intestinal Mucosa/cytology; Intestinal Mucosa/metabolism; Intestinal Mucosa/pathology; Intestinal Polyps/metabolism; Intestinal Polyps/pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear/metabolism; Trans-Activators/metabolism; Transcription Factors/metabolism; beta Catenin
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