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Comparison of liver oncogenic potential among human RAS isoforms.

DC Field Value Language
dc.contributor.author노원상-
dc.contributor.author정숙인-
dc.contributor.author조경주-
dc.date.accessioned2017-02-27T07:34:28Z-
dc.date.available2017-02-27T07:34:28Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/146919-
dc.description.abstractMutation in one of three RAS genes (i.e., HRAS, KRAS, and NRAS) leading to constitutive activation of RAS signaling pathways is considered a key oncogenic event in human carcinogenesis. Whether activated RAS isoforms possess different oncogenic potentials remains an unresolved question. Here, we compared oncogenic properties among RAS isoforms using liver-specific transgenesis in mice. Hydrodynamic transfection was performed using transposons expressing short hairpin RNA downregulating p53 and an activated RAS isoform, and livers were harvested at 23 days after gene delivery. No differences were found in the hepatocarcinogenic potential among RAS isoforms, as determined by both gross examination of livers and liver weight per body weight ratio (LW/BW) of mice expressing HRASQ61L, KRAS4BG12V and NRASQ61K. However, the tumorigenic potential differed significantly between KRAS splicing variants. The LW/BW ratio in KRAS4AG12V mice was significantly lower than in KRAS4BG12V mice (p < 0.001), and KRAS4AG12V mice lived significantly longer than KRRAS4BG12V mice (p < 0.0001). Notably, tumors from KRAS4AG12V mice displayed higher expression of the p16INK4A tumor suppressor when compared with KRAS4BG12V tumors. Forced overexpression of p16INK4A significantly reduced tumor growth in KRAS4BG12V mice, suggesting that upregulation of p16INK4A by KRAS4AG12V presumably delays tumor development driven by the latter oncogene.-
dc.description.statementOfResponsibilityopen-
dc.format.extent7354~7366-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfONCOTARGET-
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.MESHApoptosis-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarcinoma, Hepatocellular/genetics-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism-
dc.subject.MESHCarcinoma, Hepatocellular/pathology*-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCell Transformation, Neoplastic/genetics-
dc.subject.MESHCell Transformation, Neoplastic/metabolism-
dc.subject.MESHCell Transformation, Neoplastic/pathology*-
dc.subject.MESHCyclin-Dependent Kinase Inhibitor p16/metabolism-
dc.subject.MESHGTP Phosphohydrolases/genetics*-
dc.subject.MESHGTP Phosphohydrolases/metabolism-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHHumans-
dc.subject.MESHImmunoenzyme Techniques-
dc.subject.MESHLiver Neoplasms/genetics-
dc.subject.MESHLiver Neoplasms/metabolism-
dc.subject.MESHLiver Neoplasms/pathology*-
dc.subject.MESHMembrane Proteins/genetics*-
dc.subject.MESHMembrane Proteins/metabolism-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMutation/genetics*-
dc.subject.MESHProtein Isoforms-
dc.subject.MESHProto-Oncogene Proteins p21(ras)/genetics*-
dc.subject.MESHProto-Oncogene Proteins p21(ras)/metabolism-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleComparison of liver oncogenic potential among human RAS isoforms.-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeResearcher Institutes-
dc.contributor.departmentLiver Cirrhosis Clinical Research Center-
dc.contributor.googleauthorSook In Chung-
dc.contributor.googleauthorHyuk Moon-
dc.contributor.googleauthorHye-Lim Ju-
dc.contributor.googleauthorDae Yeong Kim-
dc.contributor.googleauthorKyung Joo Cho-
dc.contributor.googleauthorSilvia Ribback-
dc.contributor.googleauthorFrank Dombrowski-
dc.contributor.googleauthorDiego F. Calvisi-
dc.contributor.googleauthorSimon Weonsang Ro-
dc.identifier.doi10.18632/oncotarget.6931-
dc.contributor.localIdA03804-
dc.contributor.localIdA03640-
dc.contributor.localIdA01286-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid26799184-
dc.subject.keywordKRAS splicing variant-
dc.subject.keywordP16-INK4A-
dc.subject.keywordRAS isoform-
dc.subject.keywordhydrodynamic transfection-
dc.subject.keywordliver cancer-
dc.contributor.alternativeNameRo, Simon Weonsang-
dc.contributor.alternativeNameChung, Sook In-
dc.contributor.alternativeNameCho, Kyung Joo-
dc.contributor.affiliatedAuthorCho, Kyuong Joo-
dc.contributor.affiliatedAuthorChung, Sook In-
dc.contributor.affiliatedAuthorRo, Simon Weonsang-
dc.citation.volume7-
dc.citation.number6-
dc.citation.startPage7354-
dc.citation.endPage7366-
dc.identifier.bibliographicCitationONCOTARGET , Vol.7(6) : 7354-7366, 2016-
dc.date.modified2017-02-24-
dc.identifier.rimsid46485-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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