626 634

Cited 52 times in

Predominant Activation of JAK/STAT3 Pathway by Interleukin-6 Is Implicated in Hepatocarcinogenesis

DC Field Value Language
dc.contributor.author박승우-
dc.contributor.author박영년-
dc.contributor.author임가람-
dc.contributor.author정인혜-
dc.date.accessioned2016-02-04T11:42:31Z-
dc.date.available2016-02-04T11:42:31Z-
dc.date.issued2015-
dc.identifier.issn1522-8002-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/141021-
dc.description.abstractChronic inflammation is an important process leading to tumorigenesis. Therefore, targeting and controlling inflammation can be a promising cancer therapy. Inflammation is often caused by a variety of inflammatory cytokine such as the interleukin (IL)-6, a pleiotrophic cytokine known to be involved in the tumorigenesis. In this study, an in vivo hepatic tumorigenesis model of zebrafish was generated to demonstrate a direct consequence of the human IL6 expression causing hepatocarcinogenesis. To do this, an elevated expression of the hIL6 gene was established to specifically target the zebrafish hepatocytes by transgenesis. Interestingly, the elevated hIL6 expression caused the chronic inflammation which results in a massive infiltration of inflammatory cells. This eventually resulted in the generation of various dysplastic lesions such as clear cell, small cell, and large cell changes, and also eosinophilic and basophilic foci of hepatocellular alteration. Hepatocellular carcinoma was then developed in the transgenic zebrafish. Molecular characterization revealed upregulation of the downstream components involved in the IL6-mediated signaling pathways, especially PI3K/Akt and JAK/STAT3 pathways. Further investigation indicated that PI3K was the most reactive to the infiltrated inflammatory cells and dysplasia with large cell change, whereas STAT3 was heavily activated in the region with dysplastic foci, suggesting that the JAK/STAT3 pathway was mainly implicated in the hepatic tumorigenesis in the current model. Our present study provides an in vivo evidence of the relationship between chronic inflammation and tumorigenesis and reinforces the pivotal role of IL6 in the inflammation-associated hepatocarcinogenesis.-
dc.description.statementOfResponsibilityopen-
dc.format.extent586~597-
dc.relation.isPartOfNEOPLASIA-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAminopyridines/pharmacology-
dc.subject.MESHAnimals-
dc.subject.MESHCarcinoma, Hepatocellular/pathology*-
dc.subject.MESHCell Transformation, Neoplastic-
dc.subject.MESHCyclic S-Oxides/pharmacology-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHEnzyme Activation/drug effects-
dc.subject.MESHHumans-
dc.subject.MESHInflammation/immunology-
dc.subject.MESHInterleukin-6/genetics-
dc.subject.MESHInterleukin-6/metabolism*-
dc.subject.MESHJanus Kinases/antagonists & inhibitors-
dc.subject.MESHJanus Kinases/metabolism*-
dc.subject.MESHLiver/pathology-
dc.subject.MESHLiver Neoplasms/pathology*-
dc.subject.MESHMorpholines/pharmacology-
dc.subject.MESHNiclosamide/pharmacology-
dc.subject.MESHPhosphatidylinositol 3-Kinases/antagonists & inhibitors-
dc.subject.MESHPhosphatidylinositol 3-Kinases/metabolism-
dc.subject.MESHSTAT3 Transcription Factor/antagonists & inhibitors-
dc.subject.MESHSTAT3 Transcription Factor/metabolism*-
dc.subject.MESHSignal Transduction/drug effects-
dc.subject.MESHZebrafish-
dc.subject.MESHZebrafish Proteins/antagonists & inhibitors-
dc.subject.MESHZebrafish Proteins/metabolism*-
dc.titlePredominant Activation of JAK/STAT3 Pathway by Interleukin-6 Is Implicated in Hepatocarcinogenesis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorIn Hye Jung-
dc.contributor.googleauthorJeffrey Hyun-Kyu Choi-
dc.contributor.googleauthorYong-Yoon Chung-
dc.contributor.googleauthorGa-Lam Lim-
dc.contributor.googleauthorYoung-Nyun Park-
dc.contributor.googleauthorSeung Woo Park-
dc.identifier.doi10.1016/j.neo.2015.07.005-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01551-
dc.contributor.localIdA01563-
dc.contributor.localIdA03353-
dc.contributor.localIdA03698-
dc.relation.journalcodeJ02312-
dc.identifier.eissn1476-5586-
dc.identifier.pmid26297436-
dc.contributor.alternativeNamePark, Seung Woo-
dc.contributor.alternativeNamePark, Young Nyun-
dc.contributor.alternativeNameLeem, Ga Lam-
dc.contributor.alternativeNameJung, In Hye-
dc.contributor.affiliatedAuthorPark, Seung Woo-
dc.contributor.affiliatedAuthorPark, Young Nyun-
dc.contributor.affiliatedAuthorLeem, Ga Lam-
dc.contributor.affiliatedAuthorJung, In Hye-
dc.rights.accessRightsfree-
dc.citation.volume17-
dc.citation.number7-
dc.citation.startPage586-
dc.citation.endPage597-
dc.identifier.bibliographicCitationNEOPLASIA, Vol.17(7) : 586-597, 2015-
dc.identifier.rimsid30459-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.