Abstract
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-mLeprdb/db; Apc1638N/+ 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 Apc1638N/+ 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.
Original language | English (US) |
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Pages (from-to) | 1716-1719 |
Number of pages | 4 |
Journal | International Journal of Obesity |
Volume | 32 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2008 |
Keywords
- Apc
- Colon cancer
- Diabetes
- db/db
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics