Full metadata record
DC FieldValueLanguage
dc.contributor.authorYu, Sheng-Yien_US
dc.contributor.authorLiu, Huei-Fangen_US
dc.contributor.authorWang, Su-Peien_US
dc.contributor.authorChang, Chia-Chingen_US
dc.contributor.authorTsai, Chuan-Meien_US
dc.contributor.authorChao, Jui-Ien_US
dc.date.accessioned2014-12-08T15:30:42Z-
dc.date.available2014-12-08T15:30:42Z-
dc.date.issued2013-04-25en_US
dc.identifier.issn0009-2797en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.cbi.2013.03.011en_US
dc.identifier.urihttp://hdl.handle.net/11536/21924-
dc.description.abstractGefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy. Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells. Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression. Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer). BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins. Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells. Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels. Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells. The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells. Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectGefitiniben_US
dc.subjectSecurinen_US
dc.subjectApoptosisen_US
dc.subjectEGFRen_US
dc.subjectCancer cellsen_US
dc.titleEvidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.cbi.2013.03.011en_US
dc.identifier.journalCHEMICO-BIOLOGICAL INTERACTIONSen_US
dc.citation.volume203en_US
dc.citation.issue2en_US
dc.citation.spage412en_US
dc.citation.epage422en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000319235100005-
dc.citation.woscount3-
Appears in Collections:Articles


Files in This Item:

  1. 000319235100005.pdf