Loss of Slc26a9 induces an early gastric malignancy in mice and is associated with gastric cancer in humans

Abstract

BackgroundSlc26a9 deficiency causes a series of precancerous changes in murine stomach at 5 weeks of age (Xu et al., PNAS 2008), suggesting that Slc26a9 may be involved in gastric malignancy with increasing of age. Aim andMethodsTo understand how Slc26a9 deficiency promotes gastric carcinogenesis in mice and humans, histopathological and immunohistochemical analysis were performed in Slc26a9‐/‐ and WT stomach at 15 months of age. Slc26a9 mRNA and protein expression were measured by qPCR and Western‐blot in human normal gastric epithelium, gastric cancer tissues and cell lines.ResultsAbsence of Slc26a9 in the mouse caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancer including oxyntic atrophy, chronic inflammation independent of Hp infection, intestinal metaplasia, TFF2‐expressing metaplasia, and ultimately high‐grade intraepithelial neoplasias. Accompanying with stimulated proliferation and suppressed apoptosis in gastric epithelial cells. human gastric cancer tissues and cell lines displayed significantly decreased of Slc26a9 mRNA and protein expression when compared with health control. Immunohistochemical analysis of human superficial gastritis, atrophic gastritis, adenomatous polyp and gastric cancer indicated progressive decrease in Slc26a9 expression.ConclusionsSlc26a9 deficiency leads to spontaneous premalignant and malignant lesions in the gastric epithelia of mice and it can be as a useful model to study gastric cancer. Slc26a9 may be a candidate tumor suppressor gene in development and progression of human gastric cancer.