Alimentary TractSynergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer☆,☆☆
Section snippets
Animals
The insulin-gastrin (INS-GAS) transgenic mice have been described previously12, 13 and are free of specific pathogens. Animals were housed in a microisolator, solid-bottomed polycarbonate cages, fed a commercially prepared pelleted diet, and given water ad libitum. For time-course studies involving ECL and parietal cell numbers, serum gastrin levels, and maximal acid secretion, a minimum of 4 mice were used for each time point. For long-term studies, 8 INS-GAS mice and 18 wild-type FVB/N mice
Hypergastrinemic (INS-GAS) mice show initial increases followed by sustained decreases in acid secretion and parietal cell number
To investigate long-term effects of hypergastrinemia on the gastric mucosa, we studied INS-GAS transgenic mice, which have a chimeric transgene in which the human gastrin gene is transcribed from the rat insulin I promoter.12 These mice express human heptadecapeptide gastrin (G-17) in the pancreatic β cells, which is then secreted into the circulation. We analyzed the effects of increased gastrin secretion over time in these mice and found that the changes could be divided into 2 distinct
Discussion
This study shows that transgenic mice with moderate hypergastrinemia have increased parietal cell numbers and acid secretion up to about 4 months of age. Thereafter, parietal cell numbers and acid secretion decrease gradually and there is increased expression of TGF-α family growth factors and a progression toward gastric cancer. These processes are exacerbated by the presence of Helicobacter infection. The phenotype in hypergastrinemic transgenic mice is distinct from that in rats with
References (46)
- et al.
Hypergastrinaemia produces trophic effects in stomach but not in pancreas and intestines
Regul Pept
(1986) - et al.
Trophic effects of continuous infusion of [Leu 15]-gastrin-17 in the rat
Gastroenterology
(1990) - et al.
Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis
Gastroenterology
(1993) - et al.
Long-term sequelae of Helicobacter pylori gastritis
Lancet
(1995) - et al.
Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia
Gastroenterology
(1997) - et al.
Campylobacter pylori and duodenal ulcers: the gastrin link
Lancet
(1989) - et al.
Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with H. felis infection
Gastroenterology
(1998) - et al.
Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats
Gastroenterology
(1996) - et al.
Possible role of transforming growth factor alpha in the pathogenesis of Ménétrier's disease: supportive evidence from humans and transgenic mice
Gastroenterology
(1992) - et al.
Localization of heparin-binding epidermal growth factor–like growth factor in human gastric mucosa
Gastroenterology
(1995)
Induction of heparin binding epidermal growth factor–like growth factor and amphiregulin mRNAs by gastrin in the rat stomach
Biochem Biophys Res Commun
Helicobacter pylori infection induces gastric cancer in Mongolian gerbils
Gastroenterology
Gastrin induces heparin-binding epidermal growth factor–like growth factor in rat gastric epithelial cells transfected with gastrin receptor
Gastroenterology
Helicobacter pylori infection and chronic gastric acid hyposecretion
Gastroenterology
Processing of the gastrin precursor. Modulation of phosphorylated, sulfated, and amidated products
J Biol Chem
Effects of bombesin on the release of glycine–extended progastrin (gastrin G) in rat antral tissue culture
Gastroenterology
Purification and structural characterization of progastrin-derived peptides from a human gastrinoma
J Biol Chem
Trophic effects of gastrin
Scand J Gastroenterol
Hyperplastic gastropathy. Clinicopathologic correlation
Am J Surg Pathol
Stereologic investigations of human gastric mucosa. II. Oxyntic mucosa from patients with Zollinger–Ellison syndrome
Scand J Gastroenterol
Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety
Ann Intern Med
Helicobacter pylori related hypergastrinemia is the result of selective increase in gastrin 17
Gut
Pancreatic gastrin stimulates islet differentiation of TGF-alpha–induced ductular precursor cells
J Clin Invest
Cited by (528)
Development of amplified luminescent proximity homogeneous assay for quantitation of gastrin-17
2023, Analytical BiochemistryCarcinogenic microbiota and its role in colorectal cancer development
2022, Seminars in Cancer BiologyMolecular pathogenesis, targeted therapies, and future perspectives for gastric cancer
2022, Seminars in Cancer BiologyCitation Excerpt :Transgenic mouse models were introduced to allow researchers in the gastric cancer field more precise control over the tumor initiating events. The INS-GAS transgenic mice were designed to excessively express the gastric hormone, gastrin, under control of the insulin promoter [189,190]. These mice develop gastric atrophy, dysplasia, and gastric cancer [167].
Helicobacters and cancer, not only gastric cancer?
2022, Seminars in Cancer BiologyElevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia
2022, Cellular and Molecular Gastroenterology and Hepatology
- ☆
Address requests for reprints to: Timothy C. Wang, M.D., Massachusetts General Hospital, Gastrointestinal Unit, GRJ 724, 32 Fruit Street, Boston, Massachusetts 02114. e-mail: [email protected]; fax: (617) 726-3673.
- ☆☆
Supported by National Institutes of Health (NIH) grant RO1 CA67529 (to T.C.W. and J.G.F.), by a Veterans Administration Merit Review and NIH grants (to J.R.G.), and by Swedish MRC 32X-13108 (to D.C.).