Dietary induction of colonic tumors in a mouse model of sporadic colon cancer

Kan Yang, Naoto Kurihara, Kunhua Fan, Harold Newmark, Basil Rigas, Laura Bancroft, Georgia Corner, Elayne Livote, Martin Lesser, Winfried Edelmann, Anna Velcich, Martin Lipkin, Leonard Augenlicht

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78 Scopus citations

Abstract

A defined rodent "new Western diet" (NWD), which recapitulates intake levels of nutrients that are major dietary risk factors for human colon cancer, induced colonic tumors when fed to wild-type C57Bl/6 mice for 1.5 to 2 years from age 6 weeks (two-thirds of their life span). Colonic tumors were prevented by elevating dietary calcium and vitamin D3 to levels comparable with upper levels consumed by humans, but tumorigenesis was not altered by similarly increasing folate, choline, methionine, or fiber, each of which was also at the lower levels in the NWD that are associated with risk for colon cancer. The NWD significantly altered profiles of gene expression in the flat colonic mucosa that exhibited heterogeneity among the mice, but unsupervised clustering of the data and novel statistical analyses showed reprogramming of colonic epithelial cells in the flat mucosa by the NWD was similar to that initiated by inheritance of a mutant Apc allele. The NWD also caused general down-regulation of genes encoding enzymes involved in lipid metabolism and the tricarboxylic acid cycle in colonic epithelial cells before tumor formation, which was prevented by the supplementation of the NWD with calcium and vitamin D3 that prevented colon tumor development, demonstrating profound interaction among nutrients. This mouse model of dietary induction of colon cancer recapitulates levels and length of exposure to nutrients linked to relative risk for human sporadic colon cancer, which represents the etiology of >90% of colon cancer in the United States and other Western countries.

Original languageEnglish (US)
Pages (from-to)7803-7810
Number of pages8
JournalCancer Research
Volume68
Issue number19
DOIs
StatePublished - Oct 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yang, K., Kurihara, N., Fan, K., Newmark, H., Rigas, B., Bancroft, L., Corner, G., Livote, E., Lesser, M., Edelmann, W., Velcich, A., Lipkin, M., & Augenlicht, L. (2008). Dietary induction of colonic tumors in a mouse model of sporadic colon cancer. Cancer Research, 68(19), 7803-7810. https://doi.org/10.1158/0008-5472.CAN-08-1209