Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice Journal Article
| Authors: | Gravaghi, C.; Bo, J.; LaPerle, K. M. D.; Quimby, F.; Kucherlapati, R.; Edelmann, W.; Lamprecht, S. A. |
| Article Title: | Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice |
| 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. © 2008 Macmillan Publishers Limited All rights reserved. |
| Keywords: | controlled study; gene mutation; mutation; nonhuman; mouse; animals; mice; animal tissue; mus; animal experiment; animal model; colonic neoplasms; obesity; mice, inbred c57bl; cell transformation, neoplastic; digestive system cancer; oncogene; colon cancer; rodentia; mouse strain; gastrointestinal tract; non insulin dependent diabetes mellitus; diabetes; diabetes mellitus, type 2; colon carcinogenesis; genes, apc; apc1638n/+; db/db; apc gene; db gene |
| Journal Title: | International Journal of Obesity |
| Volume: | 32 |
| Issue: | 11 |
| ISSN: | 0307-0565 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-11-01 |
| Start Page: | 1716 |
| End Page: | 1719 |
| Language: | English |
| DOI: | 10.1038/ijo.2008.149 |
| PUBMED: | 18725892 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 17 November 2011" - "CODEN: IJOBD" - "Source: Scopus" |
