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Promoter Demethylation of WIF-1 by Epigallocatechin-3-gallate in Lung Cancer Cells

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机构: [1]Department of Cardiothoracic Surgery, Beijing Friendship Hospital [2]Thoracic Oncology Laboratory, Department of Surgery, UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0128, U.S.A. [3]Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan, R.O.C. [4]Beijing Xuanwu Hospital, Capital Medical University, Beijing, P.R.C.
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关键词: Wnt pathway Wnt inhibitory factor-1 promoter hypermethylation demethylation epigallocatechin-3-gallate EGCG

摘要:
Background: Aberrant promoter methylation of Writ inhibitory factor-1 (WIF-1) is a fundamental mechanism of epigenetic silencing in human cancers. Epigallocatechin-3-gallate (EGCG) has been reported to directly reactivate several methylation-silenced genes. The promoter demethylation and reactivation of WIF-1 has not previously been reported. Materials and Methods: Methylation-specific PCR, sequencing analysis and RT-PCR analysis were performed to evaluate promoter demethylation of WIF-1 and WIF-1 expression, Western blot analysis and luciferase reporter assay were performed to evaluate expression of cytosolic beta-catenin protein and Tcf/Lef reporter activity. Results: Promoter demethylation of WIF-1 and restoration of WIF-1 expression after EGCG treatment are demonstrated in H460 and A549 cell lines. EGCG also decreased cytosolic beta-catenin protein level and inhibited Tcf/Lef reporter activity. Conclusion: These results suggest the potential therapeutic use of EGCG for the reversal of WIF-1 promoter methylation.

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出版当年[2008]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2007]版:
Q4 ONCOLOGY
最新[2023]版:
Q4 ONCOLOGY

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第一作者机构: [1]Department of Cardiothoracic Surgery, Beijing Friendship Hospital [2]Thoracic Oncology Laboratory, Department of Surgery, UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0128, U.S.A.
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通讯机构: [*]Department of Surgery, University of California, San Francisco, Box 0128, San Francisco, CA 94143-0128, U.S.A.
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