1. Induction of follistatin precedes gastric transformation in gastrin deficient mice
- Author
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Kang, Weiqun, Saqui-Salces, Milena, Zavros, Yana, and Merchant, Juanita L.
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RODENTS , *GASTROINTESTINAL hormones , *CHOLECYSTOKININ , *GASTRIC secretions - Abstract
Abstract: We previously showed that antral gastric tumors develop in gastrin-deficient (Gas−/−) mice. Therefore Gas−/−mice were studied sequentially over 12 months to identify molecular mechanisms underlying gastric transformation. Fundic atrophy developed by 9 months in Gas−/− mice. Antral mucosal hyperplasia developed coincident with the focal loss of TFF1 and Muc5AC. Microarray analysis of 12 month Gas−/− tumors revealed an increase in follistatin, an activin/BMP antagonist. We found that elevated follistatin expression occurred in the proliferative neck zone of hyperplastic antrums, in antral tumors of Gas−/− mice, and also in human gastric cancers. Follistatin induced cyclin D1 and the trefoil factors TFF1 and TFF2 in a gastric cancer cell line. We concluded that antral hyperplasia in Gas−/− mice involves amplification of mucous cell lineages due to follistatin, suggesting its role in the development of antral gastric tumors. [Copyright &y& Elsevier]
- Published
- 2008
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