Gastrin-induced apoptosis contributes to carcinogenesis in the stomach
Authors
Cui, GuanglinTakaishi, Shigeo
Ai, Wandong
Betz, Kelly S.
Florholmen, Jon R.
Koh, Theodore J.
Houghton, JeanMarie
Pritchard, D. Mark
Wang, Timothy C.
UMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDocument Type
Journal ArticlePublication Date
2006-08-09Keywords
AnimalsApoptosis
Atrophy
Disease Models, Animal
Gastrins
Helicobacter Infections
Helicobacter felis
Male
Mice
Mice, Knockout
Proto-Oncogene Proteins c-bcl-2
Receptor, Cholecystokinin B
Receptors, Histamine H2
Stomach Neoplasms
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the stomach, but the mechanisms have not been well defined. We investigated the possible role of gastrin-induced gastric cell apoptosis in the development of gastric cancer. We examined apoptosis and the expression of Bcl-2 family proteins in INS-GAS mice of different ages, as well as in gastrin-deficient (GAS-KO) mice after gastrin-17 (G-17) infusion. In addition, we studied the effects of the gastrin/cholecystokinin-2 (CCK-2) receptor antagonist YF476 and/or histamine H2 (H-2) receptor antagonist loxtidine on apoptosis and atrophy in INS-GAS mice with or without Helicobacter felis (H. felis) infection. INS-GAS mice had age-associated increases in Bax protein expression and decreases in Bcl-2 protein expression, along with increased glandular and epithelial cell apoptosis. At 8-week gastrin infusions in GAS-KO mice resulted in a similar pattern of altered Bax and Bcl-2 expression, followed by gastric cell apoptosis. H. felis infection of INS-GAS mice led to increased apoptosis and the development of atrophy, whereas treatment with either YF476 and/or loxtidine strongly inhibited both apoptosis and atrophy. In vitro studies with Fas-expressing RGM1 cells showed that gastrin stimulation alone directly induced apoptosis via gastrin/CCK-2 receptor and synergized with FasL stimulation. These results indicate that gastrin can induce apoptosis in gastric epithelial cells and contribute to the development of gastric carcinogenesis.Source
Lab Invest. 2006 Oct;86(10):1037-51. Epub 2006 Aug 7. Link to article on publisher's siteDOI
10.1038/labinvest.3700462Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38500PubMed ID
16894354Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/labinvest.3700462