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• W1989588501 abstract "Abstract Background: Gastric neoplasia is common in humans, yet controversy remains over contributions of chronic achlorhydria, gastrinemia and hyperplasia, to cancer risk. To study this, mice lacking the gastric H/K‐ATPase ( Atp4a (–/ – ) mice) were used to determine whether chronic loss of acid secretion, with attendant hypergastrinemia, predisposes to cancer phenotype. Methods: Atp4a ( –/– ) and Atp4a (+/+) mice , paired for age and gender, were examined at 3, 8, 12 and 20 months for histopathology, and for expression of the trefoil factor family (TFF)1–3, Reg IIIβ, γ and δ, osteopontin, CD44, chromogranin A, Crp‐ductin, and galectin, all of which are important in cell growth. Results: By 8 months, the glandular stomach of the Atp4a ( –/– ) mice doubled in weight and thickness, and several modulators of growth were increased. Female Atp4a ( –/– ) mice were more hyperplastic than Atp4a ( –/– ) males at 12 and 20 months. By 1 year, severe mucocystic hyperplasia, incomplete intestinal metaplasia, ciliated metaplasia, a shift in mucins from neutral to acidic, and inflammation were widespread. Cells in the mucus pit zone developed a pyloric‐type appearance, containing large hyaline‐like, periodic acid–Schiff (PAS)‐negative/alcian blue‐negative inclusions. But critical characteristics of gastric neoplasia, such as nuclear atypia, invasion into the muscularis mucosa, and metastases were absent. In Atp4a ( –/– ) mice, chromogranin A and histidine decarboxylase, RegIIIγ and δ, TFF3, osteopontin and CD44 were upregulated while Reg IIIβ, and TFF1 were reduced. Conclusions: Chronic achlorhydria and hypergastrinemia in aged Atp4a ( –/– ) mice produced progressive hyperplasia, mucocystic and incomplete intestinal metaplasia, and the upregulation of growth factors without histological evidence of neoplasia. © 2005 Blackwell Publishing Asia Pty Ltd" @default.
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• W1989588501 date "2005-07-01" @default.
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• W1989588501 title "Gastric achlorhydria in H/K-ATPase-deficient (Atp4a(-/-)) mice causes severe hyperplasia, mucocystic metaplasia and upregulation of growth factors" @default.
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• W1989588501 doi "https://doi.org/10.1111/j.1440-1746.2005.03867.x" @default.
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