Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 조인호 | * |
dc.date.accessioned | 2016-11-30T02:11:31Z | - |
dc.date.available | 2016-11-30T02:11:31Z | - |
dc.date.issued | 2008 | * |
dc.identifier.issn | 1096-6080 | * |
dc.identifier.other | OAK-5217 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/232914 | - |
dc.description.abstract | Cadmium is a heavy metal that has multiple toxic effects on human health and has been classified as a human carcinogen. E-cadherin is a major target of cadmium; however, the roles of E-cadherin and cadmium and the mechanisms of tumor progression remain to be defined. Here, we demonstrate that cadmium increases E-cadherin processing via a γ-secretase in the T47D breast cancer cell lines. This presenilin 1 (PS1)/γ-secretase-dependent cleavage of E-cadherin was accompanied by changes in reactive oxygen species or calcium. E-cadherin cleavage was blocked by a PS1 dominant-negative mutant, γ-secretase inhibitors [N-[N-(3,5-Difluorophenacetyl-L-alanyl)]- S-phenylglycine t-butyl ester (DAPT) and L-685,486], antioxidants (N-acetylcysteine and Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride), or a calcium chelating drug 1,2-bis(o-Aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl) ester. Immunofluorescence analysis confirmed the disappearance of E-cadherin staining at the cell surface. Those inhibitors attenuated cadmium-induced cytotoxicity. Additionally, cadmium treatment increased cell motility and invasion ability, which was abated by DAPT. Interestingly, cyclooxygenase-2 (COX-2) expression induced by cadmium was also inhibited by DAPT. The cadmium-induced cell motility and invasion ability were inhibited by a COX-2 inhibitor, NS398. Our data indicate a novel molecular mechanism that links cytotoxicity of cadmium and disrupted E-cadherin processing to adherens junctions; cadmium induces COX-2 expression via γ-secretase, which increases cell motility and invasion ability. Understanding the downstream signaling cascades of cadmium that promote tumor progression might be a key to the development of novel therapeutic strategies. © The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. | * |
dc.language | English | * |
dc.title | Presenilin 1/γ-secretase is associated with cadmium-induced e-cadherin cleavage and COX-2 gene expression in T47D breast cancer cells | * |
dc.type | Article | * |
dc.relation.issue | 2 | * |
dc.relation.volume | 106 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 413 | * |
dc.relation.lastpage | 422 | * |
dc.relation.journaltitle | Toxicological Sciences | * |
dc.identifier.doi | 10.1093/toxsci/kfn197 | * |
dc.identifier.wosid | WOS:000260979800013 | * |
dc.identifier.scopusid | 2-s2.0-56649100788 | * |
dc.author.google | Park C.S. | * |
dc.author.google | Kim O.S. | * |
dc.author.google | Yun S.-M. | * |
dc.author.google | Jo S.A. | * |
dc.author.google | Jo I. | * |
dc.author.google | Koh Y.H. | * |
dc.contributor.scopusid | 조인호(26643129000;56663841900) | * |
dc.date.modifydate | 20240123112949 | * |