title: Dietary induction of colonic tumors in a mouse model of sporadic colon cancer.
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 D(3) 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 D(3) 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.
authors.affiliation: Strang Cancer Research Laboratory, Department of Medicine, Gastroenterology and Hepatology, Weill Medical College of Cornell University, New York, New York 10467, USA.
authors.forename: Kan
authors.initials: K
authors.lastname: Yang
authors.forename: Naoto
authors.initials: N
authors.lastname: Kurihara
authors.forename: Kunhua
authors.initials: K
authors.lastname: Fan
authors.forename: Harold
authors.initials: H
authors.lastname: Newmark
authors.forename: Basil
authors.initials: B
authors.lastname: Rigas
authors.forename: Laura
authors.initials: L
authors.lastname: Bancroft
authors.forename: Georgia
authors.initials: G
authors.lastname: Corner
authors.forename: Elayne
authors.initials: E
authors.lastname: Livote
authors.forename: Martin
authors.initials: M
authors.lastname: Lesser
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
authors.forename: Anna
authors.initials: A
authors.lastname: Velcich
authors.forename: Martin
authors.initials: M
authors.lastname: Lipkin
authors.forename: Leonard
authors.initials: L
authors.lastname: Augenlicht
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D017491:Genes, APC; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D018396:Mucin-1 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018396:Mucin-1