Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 24, Issue 17, Pages 7598-7611Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.17.7598-7611.2004
Keywords
-
Categories
Funding
- NCI NIH HHS [R01CA70896, R01CA86071, P30 CA51008-13, R01 CA086072, R01CA86072, R01CA75503, P30 CA051008, R01 CA070896, R01 CA075503] Funding Source: Medline
- NIA NIH HHS [R03AG20337] Funding Source: Medline
Ask authors/readers for more resources
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 (Apc(Min)) develop intestinal adenomas. Here, the crossing of Apc(Min) 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 Apc(Min)/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available