title: Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice.
abstract: Patients with ulcerative colitis are at risk for colon cancer and frequently have microsatellite instability,which, in turn, is usually associated with inactivation of transforming growth factor (TGF) beta signaling. TGF-beta1 deficiency in mice can lead to colon cancer that is preceded by precancerous lesions having submucosal inflammation and hyperplastic crypts. Germ-free TGF-beta1-deficient mice are free of inflammation, hyperplasia, and cancer, but when reintroduced into a Helicobacter hepaticus-containing specific pathogen-free room, these lesions reappear. Because adenoma/carcinoma but not inflammation/hyperplasia is dependent on the genetic backgrounds tested, colitis is required, but not sufficient, for carcinogenesis. This animal model should provide insight into the protective role of TGF-beta1 in early stages of ulcerative colitis-associated human colon cancer.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Engle
authors.forename: Ilona
authors.initials: I
authors.lastname: Ormsby
authors.forename: Sharon
authors.initials: S
authors.lastname: Pawlowski
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Boivin
authors.forename: Joanne
authors.initials: J
authors.lastname: Croft
authors.forename: Edward
authors.initials: E
authors.lastname: Balish
authors.forename: Tom
authors.initials: T
authors.lastname: Doetschman
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics / Q000382:microbiology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D005856:Germ-Free Life; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1