Elimination of Colon Cancer in Germ-free Transforming Growth Factor Beta 1-deficient Mice

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.