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Am J Physiol Gastrointest Liver Physiol (December 28, 2006). doi:10.1152/ajpgi.00269.2006
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Submitted on June 19, 2006
Accepted on December 25, 2006

Long term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/{beta}-catenin signaling in rats

Takehiro Fujise1, Ryuichi Iwakiri1, Takashi Kakimoto1, Ryosuke Shiraishi1, Yasuhisa Sakata1, Bin Wu1, Seiji Tsunada1, Akihumi Ootani1, and Kazuma Fujimoto1*

1 Internal Medicine, Saga Medical School, Saga, Japan

* To whom correspondence should be addressed. E-mail: fujimoto{at}med.saga-u.ac.jp.

The Wnt signaling pathway plays an essential role and, amount of fat intake and composition of dietary fatty acids are crucial factors for colon carcinogenesis. We investigated whether various dietary fats affected the Wnt signaling pathway of colon tumorigenesis in azoxymethane (AOM)-treated rats. Male SD rats were given intraperitonial injections of AOM and supplemented with 10% corn, olive, beef, and fish oil for 44 weeks. Aberrant crypt foci (ACF) and tumors were examined at 12 and 44 weeks. Normal appearing colon mucosal proliferation and apoptosis were evaluated by BrdU incorporation, and %fragmented DNA, respectively. Expression of {beta}-catenin, cyclinD1, Wnt2, Wint3, and Wnt5a of normal appearing colon mucosa were analyzed by Western blotting. Long-term dietary corn oil and beef tallow increased ACF, tumor incidence and tumor number in AOM-treated rats. In contrast, both olive and fish oil inhibited them. Dietary corn oil and beef tallow increased BrdU incorporation and expression of cytosolic {beta}-catenin and cyclin D1, and decreased apoptosis in the colon mucosa. Expression of Wnt2 and Wnt3, in rats fed with beef tallow, and Wnt5a, in rats fed with corn oil, increased with or without AOM-treatment. BrdU-incorporated cells were often observed at tops of crypts in rats fed with beef tallow, while this was not observed in rats fed with other diet. Long-term high intake of corn oil and beef tallow enhanced cell proliferation through Wnt signaling and modulated distribution of progenitor cells, which might contributed to promotimg effect in colon tumorigenesis.




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