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Gastric Epithelial Reactive Oxygen Species Prevent Normoxic Degradation of Hypoxia-inducible Factor-1α in Gastric Cancer Cells : Gastric epithelial reactive oxygen species prevent normoxic degradation of hypoxia-inducible factor-1 alpha in gastric cancer cells
DC Field | Value | Language |
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dc.contributor.author | Park, Jung-Hyun | - |
dc.contributor.author | Kim, Tae You | - |
dc.contributor.author | Jong, Hyun-Soon | - |
dc.contributor.author | Kim, Tai Young | - |
dc.contributor.author | Chun, Yang-Sook | - |
dc.contributor.author | Park, Jong-Wan | - |
dc.contributor.author | Lee, Choon-Taek | - |
dc.contributor.author | Jung, Hyun Chae | - |
dc.contributor.author | Kim, Noe Kyeong | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.date.accessioned | 2021-01-31T11:07:53Z | - |
dc.date.available | 2021-01-31T11:07:53Z | - |
dc.date.created | 2020-12-16 | - |
dc.date.issued | 2003-01 | - |
dc.identifier.citation | Clinical Cancer Research, Vol.9 No.1, pp.433-440 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.other | 119242 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173044 | - |
dc.description.abstract | The expression of hypoxia inducible factor (HIF)-1alpha protein is tightly regulated by cellular oxygen status. Namely, HIF-1alpha protein is degraded rapidly in normoxic cells, whereas hypoxia stabilizes HIF-1alpha to transactivate hypoxia-responsive genes. Here we show that HIF-1alpha protein is expressed aberrantly in gastric cancer cells under normoxia in a reactive oxygen species (ROS)-dependent manner. The normoxic expression of HIF-1alpha in concordance with its DNA binding activity enhances the transcription of target genes such as vascular endothelial growth factor. The aberrant normoxic expression of HIF-1alpha is not associated with genetic abnormalities such as the loss of von Hippel-Lindau tumor suppressor, but is well correlated with endogenous ROS (hydrogen peroxide) generation. HIF-1alpha expression is blocked by nonmitochondrial ROS inhibitors, but not by inhibitors of mitochondrial electron transfer, which indicates that nonmitochondrial ROS stabilize HIF-1alpha protein in these cells. Gastric epithelial ROS have been linked to Helicobacter pylori-induced gastric carcinogenesis. This study demonstrates for the first time that ROS from H. pylori-infected gastric epithelial cells induce HIF-1alpha expression and subsequently activate HIF-1alpha-mediated transcription. Taken together, these results provide a novel mechanism of HIF-1alpha stabilization in gastric cancer, and demonstrate that gastric epithelial ROS, endogenously generated or H. pylori-stimulated, lead to the constant expression of HIF-1alpha protein under normoxia. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | Gastric Epithelial Reactive Oxygen Species Prevent Normoxic Degradation of Hypoxia-inducible Factor-1α in Gastric Cancer Cells | - |
dc.title.alternative | Gastric epithelial reactive oxygen species prevent normoxic degradation of hypoxia-inducible factor-1 alpha in gastric cancer cells | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.citation.journaltitle | Clinical Cancer Research | - |
dc.identifier.wosid | 000180430600053 | - |
dc.identifier.scopusid | 2-s2.0-12244267687 | - |
dc.citation.endpage | 440 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 433 | - |
dc.citation.volume | 9 | - |
dc.identifier.sci | 000180430600053 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kim, Tae You | - |
dc.contributor.affiliatedAuthor | Chun, Yang-Sook | - |
dc.contributor.affiliatedAuthor | Park, Jong-Wan | - |
dc.contributor.affiliatedAuthor | Lee, Choon-Taek | - |
dc.contributor.affiliatedAuthor | Jung, Hyun Chae | - |
dc.contributor.affiliatedAuthor | Kim, Noe Kyeong | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR PROTEIN | - |
dc.subject.keywordPlus | HELICOBACTER-PYLORI INFECTION | - |
dc.subject.keywordPlus | UBIQUITIN-PROTEASOME PATHWAY | - |
dc.subject.keywordPlus | FACTOR 1-ALPHA | - |
dc.subject.keywordPlus | PROLINE HYDROXYLATION | - |
dc.subject.keywordPlus | PROLYL HYDROXYLATION | - |
dc.subject.keywordPlus | HIF-ALPHA | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordPlus | VHL | - |
dc.subject.keywordPlus | HIF-1-ALPHA | - |
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