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Cited 46 times in

Definition of Ubiquitination Modulator COP1 as a Novel Therapeutic Target in Human Hepatocellular Carcinoma

DC FieldValueLanguage
dc.contributor.author송호택-
dc.contributor.author이윤한-
dc.date.accessioned2015-04-23T17:52:26Z-
dc.date.available2015-04-23T17:52:26Z-
dc.date.issued2010-
dc.identifier.issn0008-5472-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/103300-
dc.description.abstractThe development of targeted therapeutics for hepatocellular carcinoma (HCC) remains a major challenge. The ubiquitination modulator COP1 regulates p53 activity by ubiquitination and it is frequently overexpressed in human HCC. In this study, we tested the hypothesis that COP1 blockade by short interfering RNA (siRNA)-mediated inhibition could affect the course of HCC progression. The COP1 isoform COP1-1 was selected as the most effective target for siRNAs in terms of growth inhibition and apoptotic induction in several HCC cell lines. Growth inhibition occurred in HCC cells that retained wild-type p53 or expressed mutant p53 (Y220C or R249S), whereas p53-null Hep3B cells were resistant. Microarray expression analysis revealed that the antiproliferative effects of COP1 blockade were driven by a common subset of molecular alterations including a p53-associated functional network. In an orthotopic mouse xenograft model of HCC, systemic delivery of a modified COP1 siRNA by stable nucleic acid-lipid particles suppressed neoplastic growth in liver without unwanted immune responses. Our findings offer a first proof of principle that COP1 can be a promising target for systemic therapy of HCC.-
dc.description.statementOfResponsibilityopen-
dc.format.extent8264~8269-
dc.relation.isPartOfCANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBiomarkers, Tumor/genetics-
dc.subject.MESHBiomarkers, Tumor/metabolism-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarcinoma, Hepatocellular/genetics-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism*-
dc.subject.MESHCarcinoma, Hepatocellular/prevention & control*-
dc.subject.MESHCell Cycle-
dc.subject.MESHGene Expression Profiling-
dc.subject.MESHHumans-
dc.subject.MESHLiver Neoplasms/genetics-
dc.subject.MESHLiver Neoplasms/metabolism*-
dc.subject.MESHLiver Neoplasms/prevention & control*-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, SCID-
dc.subject.MESHMutation/genetics-
dc.subject.MESHOligonucleotide Array Sequence Analysis-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRNA, Small Interfering/pharmacology-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHTransplantation, Heterologous-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHTumor Suppressor Protein p53/genetics-
dc.subject.MESHTumor Suppressor Protein p53/metabolism-
dc.subject.MESHUbiquitin/metabolism*-
dc.subject.MESHUbiquitin-Protein Ligases/antagonists & inhibitors-
dc.subject.MESHUbiquitin-Protein Ligases/genetics-
dc.subject.MESHUbiquitin-Protein Ligases/metabolism*-
dc.subject.MESHUbiquitination-
dc.titleDefinition of Ubiquitination Modulator COP1 as a Novel Therapeutic Target in Human Hepatocellular Carcinoma-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Radiology (영상의학)-
dc.contributor.googleauthorYun-Han Lee-
dc.contributor.googleauthorJesper B. Andersen-
dc.contributor.googleauthorHo-Taek Song-
dc.contributor.googleauthorAdam D. Judge-
dc.contributor.googleauthorDaekwan Seo-
dc.contributor.googleauthorTsuyoshi Ishikawa-
dc.contributor.googleauthorJens U. Marquardt-
dc.contributor.googleauthorMitsuteru Kitade-
dc.contributor.googleauthorMarian Durkin1, Chiara Raggi-
dc.contributor.googleauthorHyun Goo Woo-
dc.contributor.googleauthorElizabeth A. Conner-
dc.contributor.googleauthorItzhak Avital-
dc.contributor.googleauthorIan MacLachlan-
dc.contributor.googleauthorValentina M. Factor-
dc.contributor.googleauthorSnorri S. Thorgeirsson-
dc.identifier.doi10.1158/0008-5472.CAN-10-0749-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02080-
dc.contributor.localIdA03029-
dc.relation.journalcodeJ00452-
dc.identifier.eissn1538-7445-
dc.identifier.pmid20959491-
dc.contributor.alternativeNameSong, Ho Taek-
dc.contributor.alternativeNameLee, Yun Han-
dc.contributor.affiliatedAuthorSong, Ho Taek-
dc.contributor.affiliatedAuthorLee, Yun Han-
dc.citation.volume70-
dc.citation.number21-
dc.citation.startPage8264-
dc.citation.endPage8269-
dc.identifier.bibliographicCitationCANCER RESEARCH, Vol.70(21) : 8264-8269, 2010-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers

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