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- Title
Conditional loss of TGF-β signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice.
- Authors
Hahm, K‐B.; Lee, K. M.; Kim, Y. B.; Hong, W. S.; Lee, W. H.; Han, S. U.; Kim, M. W.; Ahn, B. O.; Oh, T. Y.; Lee, M. H.; Green, J.; Kim, S. J.
- Abstract
Background: Downregulation of TGF-β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF-β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis. Methods: We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF-β type II receptor was expressed under the control of tissue-specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA[sup +] and VacA[sup +] ) or administered with azoxymethane to determine the significance of loss of TGF-β signalling in gastrointestinal carcinogenesis. Results: Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild-type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF-β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen-labelling index when infected with H.pylori than wild-type littermates (P < 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF–dnRII mice showed significantly higher incidences of ACF and colon cancers than wild-type littermates. Conclusions: Maintaining normal TGF-β signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.
- Subjects
CELL receptors; STOMACH cancer
- Publication
Alimentary Pharmacology & Therapeutics, 2002, Vol 16, p115
- ISSN
0269-2813
- Publication type
Article
- DOI
10.1046/j.1365-2036.16.s2.3.x