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Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia

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Item Type:Article
Title:Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia
Creators Name:Roepke, T.K. and Purtell, K. and King, E.C. and La Perle, K.M. and Lerner, D.J. and Abbott, G.W.
Abstract:Gastric cancer is the second leading cause of cancer death worldwide. Predisposing factors include achlorhydria, Helicobacter pylori infection, oxyntic atrophy and TFF2-expressing metaplasia. In parietal cells, apical potassium channels comprising the KCNQ1 alpha subunit and the KCNE2 beta subunit provide a K(+) efflux current to facilitate gastric acid secretion by the apical H(+)K(+)ATPase. Accordingly, genetic deletion of murine Kcnq1 or Kcne2 impairs gastric acid secretion. Other evidence has suggested a role for KCNE2 in human gastric cancer cell proliferation, independent of its role in gastric acidification. Here, we demonstrate that 1-year-old Kcne2(-/-) mice in a pathogen-free environment all exhibit a severe gastric preneoplastic phenotype comprising gastritis cystica profunda, 6-fold increased stomach mass, increased Ki67 and nuclear Cyclin D1 expression, and TFF2- and cytokeratin 7-expressing metaplasia. Some Kcne2(-/-) mice also exhibited pyloric polypoid adenomas extending into the duodenum, and neoplastic invasion of thin walled vessels in the sub-mucosa. Finally, analysis of human gastric cancer tissue indicated reduced parietal cell KCNE2 expression. Together with previous findings, the results suggest KCNE2 disruption as a possible risk factor for gastric neoplasia.
Keywords:Cell Line, Cyclin D1, Fluorescent Antibody Technique, Gastric Mucosa, Gastritis, Gene Deletion, H(+)-K(+)-Exchanging ATPase, Immunohistochemistry, KCNQ1 Potassium Channel, Ki-67 Antigen, Metaplasia, Peptides, Stomach Neoplasms, Tumor Cell Line, Voltage-Gated Potassium Channels, Western Blotting, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e11451
Date:6 July 2010
Official Publication:https://doi.org/10.1371/journal.pone.0011451
PubMed:View item in PubMed

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