Department of Anesthesiology

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Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia.

TitleTargeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia.
Publication TypeJournal Article
Year of Publication2010
AuthorsRoepke TK, Purtell K, King EC, La Perle KMD, Lerner DJ, Abbott GW
JournalPLoS One
Volume5
Issue7
Paginatione11451
Date Published2010
ISSN1932-6203
KeywordsAnimals, Blotting, Western, Cell Line, Cell Line, Tumor, Cyclin D1, Fluorescent Antibody Technique, Gastric Mucosa, Gastritis, Gene Deletion, H(+)-K(+)-Exchanging ATPase, Humans, Immunohistochemistry, KCNQ1 Potassium Channel, Ki-67 Antigen, Metaplasia, Mice, Mice, Mutant Strains, Peptides, Potassium Channels, Voltage-Gated, Stomach Neoplasms
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.

DOI10.1371/journal.pone.0011451
Alternate JournalPLoS ONE
PubMed ID20625512
PubMed Central IDPMC2897890
Grant ListR01 HL079275 / HL / NHLBI NIH HHS / United States