Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia.
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 p...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-07-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2897890?pdf=render |
| _version_ | 1819110975114051584 |
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| author | Torsten K Roepke Kerry Purtell Elizabeth C King Krista M D La Perle Daniel J Lerner Geoffrey W Abbott |
| author_facet | Torsten K Roepke Kerry Purtell Elizabeth C King Krista M D La Perle Daniel J Lerner Geoffrey W Abbott |
| author_sort | Torsten K Roepke |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T03:50:15Z |
| format | Article |
| id | doaj.art-eb9ee109b51f4099a945ce6ce58a15aa |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T03:50:15Z |
| publishDate | 2010-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eb9ee109b51f4099a945ce6ce58a15aa2022-12-21T18:40:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-07-0157e1145110.1371/journal.pone.0011451Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia.Torsten K RoepkeKerry PurtellElizabeth C KingKrista M D La PerleDaniel J LernerGeoffrey W AbbottGastric 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.http://europepmc.org/articles/PMC2897890?pdf=render |
| spellingShingle | Torsten K Roepke Kerry Purtell Elizabeth C King Krista M D La Perle Daniel J Lerner Geoffrey W Abbott Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. PLoS ONE |
| title | Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. |
| title_full | Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. |
| title_fullStr | Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. |
| title_full_unstemmed | Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. |
| title_short | Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. |
| title_sort | targeted deletion of kcne2 causes gastritis cystica profunda and gastric neoplasia |
| url | http://europepmc.org/articles/PMC2897890?pdf=render |
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