Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 배윤수 | * |
dc.date.accessioned | 2016-08-28T12:08:07Z | - |
dc.date.available | 2016-08-28T12:08:07Z | - |
dc.date.issued | 2010 | * |
dc.identifier.issn | 0016-5085 | * |
dc.identifier.other | OAK-6488 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/220715 | - |
dc.description.abstract | Background & Aims: Acquisition of resistance to the antiproliferative effect of transforming growth factor (TGF)-β1 is crucial for the malignant progression of cancers. In this study, we sought to determine whether deregulated expression of tristetrapolin (TTP), a negative posttranscriptional regulator of c-Myc, confers resistance to the antiproliferative effects of TGF-β1 on liver cancer cells. Methods: The epigenetics of TTP promoter regulation and its effects on TGF-β1 signaling were examined in hepatocellular carcinoma (HCC) cell lines and patient tissues. Results: TTP was down-regulated in HCC cell lines (10/11), compared with normal liver, as well as in tumor tissues (19/24) from paired HCC specimens. Methylation of a specific single CpG site located within the TGF-β1-responsive region (TRR) of the TTP promoter was significantly associated with TTP down-regulation in both HCC cell lines and tumor tissues (r = -0.606383, P < .001). The singly methylated CpG site was specifically bound by a transcriptional repressor complex consisting of MECP2/c-Ski/DNMT3A and abolished the TGF-β1-induced as well as basal-level expression of TTP. The epigenetic inactivation of TTP led to an increased half-life of c-Myc mRNA and blocked the cytostatic effect of TGF-β1. Statistically significant correlations were observed between the single CpG site methylation and expression levels of TTP or c-Myc in clinical samples of HCC. Conclusions: Abrogation of the post-transcriptional regulation of c-Myc via methylation of a specific single CpG site in the TTP promoter presents a novel mechanism for the gain of selective resistance to the antiproliferative signaling of TGF-β1 in HCC. © 2010 AGA Institute. | * |
dc.language | English | * |
dc.title | Functional Switching of TGF-β1 Signaling in Liver Cancer via Epigenetic Modulation of a Single CpG Site in TTP Promoter | * |
dc.type | Article | * |
dc.relation.issue | 5 | * |
dc.relation.volume | 138 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 1898 | * |
dc.relation.lastpage | 1908000000000000 | * |
dc.relation.journaltitle | Gastroenterology | * |
dc.identifier.doi | 10.1053/j.gastro.2009.12.044 | * |
dc.identifier.wosid | WOS:000276992600036 | * |
dc.identifier.scopusid | 2-s2.0-77951667118 | * |
dc.author.google | Sohn B.H. | * |
dc.author.google | Park I.Y. | * |
dc.author.google | Lee J.J. | * |
dc.author.google | Yang S. | * |
dc.author.google | Jang Y.J. | * |
dc.author.google | Park K.C. | * |
dc.author.google | Kim D.J. | * |
dc.author.google | Lee D.C. | * |
dc.author.google | Sohn H.A. | * |
dc.author.google | Kim T.W. | * |
dc.author.google | Yoo H. | * |
dc.author.google | Choi J.Y. | * |
dc.author.google | Bae Y.S. | * |
dc.author.google | Yeom Y.I. | * |
dc.contributor.scopusid | 배윤수(15031067200) | * |
dc.date.modifydate | 20240415133331 | * |