Basic-alimentary tractGastric cancer development in mice lacking the SHP2 binding site on the IL-6 family co-receptor gp130☆
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Mice
gp130757F/F mice were developed as previously described.7 Briefly, a “knock-in” mutation was generated such that amino acid substitutions Y757F and V760A were introduced into the gp130 gene. All mice were kept on a 129 Sv-J/C57BL/6 mixed background, and control age-matched mice were littermates. Mice were housed in a standard animal facility that has been shown to be free of H. pylori infection. All animal experiments were performed with the approval of the Melbourne Health Directorate Animal
Age-dependent development of gastric adenomas in gp130757F/F mice
Lesions in the stomachs of gp130757F/F mice develop with 100% penetrance in a predictable, age-dependent manner. By 6 weeks of age, discrete adenomas were macroscopically evident, usually just proximal to the pylorus, and this was often accompanied by focal gastric ulceration coincident with the adenoma itself (Figure 1B). In older animals, adenomas had increased in number, become significantly larger, and more heavily vascularized and were no longer restricted to the antrum but were also
Discussion
The gp130757F/F mouse was originally developed to genetically dissect the contribution of the SHP-2/Erk pathway in mediating intracellular signals elicited by IL-6 family cytokines. An unexpected finding was the rapid and fully penetrant development of distal stomach tumors, resulting from the loss of gp130-dependent SHP-2/Erk/AP-1 signaling. This is accompanied by exaggerated STAT3 activation because of disruption of negative reciprocal regulation of the 2 pathways.7 In this study, we have
References (39)
- et al.
Recent advances in cancer researchmouse models of tumorigenesis
Biochim Biophys Acta
(2002) - et al.
Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer
Gastroenterology
(2000) - et al.
Causal relationship between the loss of RUNX3 expression and gastric cancer
Cell
(2002) - et al.
Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies
Gastroenterology
(1989) - et al.
Association of spasmolytic polypeptide-expressing metaplasia with carcinogen administration and oxyntic atrophy in rats
Lab Invest
(2002) - et al.
Gastrin deficiency results in altered gastric differentiation and decreased colonic proliferation in mice
Gastroenterology
(1997) - et al.
Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection
Gastroenterology
(1998) - et al.
Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology
Gastroenterology
(1995) - et al.
Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium
Lab Invest
(2001) - et al.
Somatic mutations of the trefoil factor family 1 gene in gastric cancer
Gastroenterology
(2000)
Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice
Gastroenterology
Transcriptional activation of the rat vesicular monoamine transporter 2 promoter in gastric epithelial cellsregulation by gastrin
J Biol Chem
The leptin receptor
J Biol Chem
Antral mucosa expresses functional leptin receptors coupled to STAT-3 signaling, which is involved in the control of gastric secretions in the rat
Gastroenterology
Reg protein is over expressed in gastric cancer cells, where it activates a signal transduction pathway that converges on ERK1/2 to stimulate growth
FEBS Lett
The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis
Gastroenterology
Mutations of Reg Iα are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia
Gastroenterology
Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000
BMC Cancer
Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein
Science
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Supported by grants from the National Health and Medical Research Council of Australia.
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L.M.J. and B.M.A. contributed equally to this work.