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TNF-α induces expression of urokinase-type plasminogen activator and β-catenin activation through generation of ROS in human breast epithelial cells : TNF-alpha induces expression of urokinase-type plasminogen activator and beta-catenin activation through generation of ROS in human breast epithelial cells
DC Field | Value | Language |
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dc.contributor.author | Kim, Min-Jung | - |
dc.contributor.author | Kim, Do-Hee | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T09:21:03Z | - |
dc.date.available | 2021-01-31T09:21:03Z | - |
dc.date.created | 2017-11-15 | - |
dc.date.issued | 2010-12 | - |
dc.identifier.citation | Biochemical Pharmacology, Vol.80 No.12, pp.2092-2100 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.other | 2443 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172594 | - |
dc.description.abstract | Malignant tumors have a capability to degrade the extracellular matrix (ECM) by controlled proteolysis. One of the important components of the proteolysis system involved in such process is urokinase-type plasminogen activator (uPA). Tumor necrosis factor (TNF)-alpha was found to stimulate uPA. TNF-alpha impaired the ability of cells to aggregate and to attain compaction. Dyscohesion (cell-cell dissociation) induced by TNF-alpha was associated with the disordered expression of cadherin/beta-catenin at the sites of cell-cell contact. We observed that human breast epithelial (MCF-10A) cells treated with TNF-alpha transiently up-regulated expression of uPA and its mRNA transcript. In addition, TNF-alpha induced activation of beta-catenin in MCF-10A cells. Based on these findings, we attempted to examine the role of beta-catenin and its partner, Tcf-4 in upregulation of uPA. siRNA knock down of beta-catenin abrogated TNF-alpha-induced uPA expression as well as Tcf-4/beta-catenin DNA binding. TNF-alpha-stimulated MCF-10A cells exhibited increased intracellular accumulation of reactive oxygen species (ROS). TNF-alpha-induced expression of uPA and activation of beta-catenin signaling appear to be mediated by ROS in MCF-10A cells, as both events were blocked by the antioxidant N-acetylcysteine. Eupatilin (5,7-dihydroxy-3',4',6-tri-methoxy-flavone), a pharmacologically active flavone derived from Artemisia asiatica, has been shown to possess strong antioxidative activity. Eupatilin inhibited TNF-alpha-induced intracellular ROS accumulation, expression of uPA and beta-catenin activation. Moreover, eupatilin inhibited the TNF-alpha-induced invasion of MCF-10A cells. Taken together, the above results suggest that eupatilin has chemopreventive effects on mammary tumorigenesis by targeting the beta-catenin-uPA axis stimulated by TNF-alpha. (C) 2010 Published by Elsevier Inc. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | TNF-α induces expression of urokinase-type plasminogen activator and β-catenin activation through generation of ROS in human breast epithelial cells | - |
dc.title.alternative | TNF-alpha induces expression of urokinase-type plasminogen activator and beta-catenin activation through generation of ROS in human breast epithelial cells | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1016/j.bcp.2010.08.014 | - |
dc.citation.journaltitle | Biochemical Pharmacology | - |
dc.identifier.wosid | 000284177400034 | - |
dc.identifier.scopusid | 2-s2.0-78049418467 | - |
dc.citation.endpage | 2100 | - |
dc.citation.number | 12 | - |
dc.citation.startpage | 2092 | - |
dc.citation.volume | 80 | - |
dc.identifier.sci | 000284177400034 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | CARCINOMA-CELLS | - |
dc.subject.keywordPlus | CANCER INVASION | - |
dc.subject.keywordPlus | TUMOR INVASION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordAuthor | Metastasis | - |
dc.subject.keywordAuthor | TNF-alpha | - |
dc.subject.keywordAuthor | ROS | - |
dc.subject.keywordAuthor | MCF-10A cells | - |
dc.subject.keywordAuthor | uPA | - |
dc.subject.keywordAuthor | beta-Catenin | - |
dc.subject.keywordAuthor | Eupatilin | - |
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