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| Item Type: | Article |
|---|---|
| Title: | Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia |
| Creators Name: | Roepke, T.K., Purtell, K., King, E.C., La Perle, K.M., 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 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 5 |
| Number: | 7 |
| 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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