ISSN:
1365-2036
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.〈section xml:id="abs1-2"〉〈title type="main"〉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+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF-β signalling in gastrointestinal carcinogenesis.〈section xml:id="abs1-3"〉〈title type="main"〉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.〈section xml:id="abs1-4"〉〈title type="main"〉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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2036.16.s2.3.x
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