Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 32, Issue 11, Pages 1716-1719Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ijo.2008.149
Keywords
diabetes; colon cancer; Apc(1638N/+); db/db
Categories
Funding
- National Institutes of Health [CA-84301]
- National Cancer Institute [RO1 CA76329, U54 CA100926]
- The Irving Weinstein Foundation, Inc. USA
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Epidemiological evidence indicates a link between obesity and human colon cancer. A putative association between obesity and colon tumorigenesis has been explored experimentally using chemical carcinogens administered to obese rodents. The main objective of this study was to generate a new mouse line that displays both obesity and intestinal tumorigenesis. To this end, we have generated C57BLKS-mLepr(db/db); Apc(1638N/+) mice combining both db and Apc mutations. The db mutation results in obesity and type 2 diabetes, the Apc mutation is a key initiating event of intestinal neoplasia. All mice were euthanized at 6 months of age and all regions of the gastrointestinal tract examined for tumors. The results show that the combination of Apc(1638N/+) and db mutations not only enhanced mutant Apc-driven small intestinal tumorigenesis but also induced gastric and colonic tumors. Homozygous db mice did not develop gastrointestinal neoplasia. These findings indicate that obesity associated with type 2 diabetes promotes gastrointestinal tumorigenesis in Apc-deficient mice and provides evidence of a mechanistic link between obesity and colorectal neoplasia.
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