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The basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential

DC FieldValueLanguage
dc.contributor.author김상운-
dc.date.accessioned2016-02-04T11:32:53Z-
dc.date.available2016-02-04T11:32:53Z-
dc.date.issued2015-
dc.identifier.issn0885-3177-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140670-
dc.description.abstractOBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) initiates from quiescent acinar cells that attain a Kras mutation, lose signaling from basic helix-loop-helix (bHLH) transcription factors, undergo acinar-ductal metaplasia, and rapidly acquire increased growth potential. We queried whether PDA cells can be reprogrammed to revert to their original quiescent acinar cell state by shifting key transcription programs. METHODS: Human PDA cell lines were engineered to express an inducible form of the bHLH protein E47. Gene expression, growth, and functional studies were investigated using microarray, quantitative polymerase chain reaction, immunoblots, immunohistochemistry, small interfering RNA, chromatin immunoprecipitation analyses, and cell transplantation into mice. RESULTS: In human PDA cells, E47 activity triggers stable G0/G1 arrest, which requires the cyclin-dependent kinase inhibitor p21 and the stress response protein TP53INP1. Concurrently, E47 induces high level expression of acinar digestive enzymes and feed forward activation of the acinar maturation network regulated by the bHLH factor MIST1. Moreover, induction of E47 in human PDA cells in vitro is sufficient to inhibit tumorigenesis. CONCLUSIONS: Human PDA cells retain a high degree of plasticity, which can be exploited to induce a quiescent acinar cell state with reduced tumorigenic potential. Moreover, bHLH activity is a critical node coordinately regulating human PDA cell growth versus cell fate.-
dc.description.statementOfResponsibilityopen-
dc.format.extent718~727-
dc.relation.isPartOfPancreas-
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.MESHBasic Helix-Loop-Helix Transcription Factors/genetics-
dc.subject.MESHBasic Helix-Loop-Helix Transcription Factors/metabolism*-
dc.subject.MESHCarcinoma, Pancreatic Ductal/genetics-
dc.subject.MESHCarcinoma, Pancreatic Ductal/metabolism*-
dc.subject.MESHCarcinoma, Pancreatic Ductal/pathology-
dc.subject.MESHCarcinoma, Pancreatic Ductal/prevention & control-
dc.subject.MESHCell Cycle Checkpoints-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCellular Reprogramming*-
dc.subject.MESHCellular Senescence*-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHGenetic Therapy-
dc.subject.MESHHumans-
dc.subject.MESHMice, SCID-
dc.subject.MESHPancreatic Neoplasms/genetics-
dc.subject.MESHPancreatic Neoplasms/metabolism*-
dc.subject.MESHPancreatic Neoplasms/pathology-
dc.subject.MESHPancreatic Neoplasms/prevention & control-
dc.subject.MESHPhenotype-
dc.subject.MESHRNA Interference-
dc.subject.MESHTime Factors-
dc.subject.MESHTransfection-
dc.subject.MESHUp-Regulation-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleThe basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Obstetrics & Gynecology (산부인과학)-
dc.contributor.googleauthorSangWun Kim-
dc.contributor.googleauthorReyhaneh Lahmy-
dc.contributor.googleauthorChelsea Riha-
dc.contributor.googleauthorChalleng Yang-
dc.contributor.googleauthorBrad L. Jakubison-
dc.contributor.googleauthorJaco van Niekerk-
dc.contributor.googleauthorClaudio Staub-
dc.contributor.googleauthorYifan Wu-
dc.contributor.googleauthorKeith Gates-
dc.contributor.googleauthorDuc Si Dong-
dc.contributor.googleauthorStephen F. Konieczny-
dc.contributor.googleauthorPamela Itkin-Ansari-
dc.identifier.doi10.1097/MPA.0000000000000328-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00526-
dc.relation.journalcodeJ02463-
dc.identifier.pmid25894862-
dc.subject.keywordpancreatic ductal adenocarcinoma-
dc.subject.keywordID3-
dc.subject.keywordbHLH signaling-
dc.subject.keywordE47-
dc.subject.keywordreprogramming-
dc.contributor.alternativeNameKim, Sang Wun-
dc.contributor.affiliatedAuthorKim, Sang Wun-
dc.rights.accessRightsfree-
dc.citation.volume44-
dc.citation.number5-
dc.citation.startPage718-
dc.citation.endPage727-
dc.identifier.bibliographicCitationPancreas, Vol.44(5) : 718-727, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers

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