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.
基金:
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 CA 093708-01A3]; Larry Hall memorial trust; Farrise Foundation; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA093708] Funding Source: NIH RePORTER
第一作者单位:[1]Univ Calif San Francisco, Dept Surg, Ctr Comprehens Canc, Thorac Oncol Lab, San Francisco, CA 94143 USA[2]Beijing Friendship Hosp, Dept Cardiothorac Surg, Beijing, Peoples R China
通讯作者:
通讯机构:[1]Univ Calif San Francisco, Dept Surg, Ctr Comprehens Canc, Thorac Oncol Lab, San Francisco, CA 94143 USA[*1]Univ Calif San Francisco, Dept Surg, Ctr Comprehens Canc, Thorac Oncol Lab, Box 0128, San Francisco, CA 94143 USA
推荐引用方式(GB/T 7714):
Gao Zhi,Xu Zhidong,Hung Ming-Szu,et al.Promoter Demethylation of WIF-1 by Epigallocatechin-3-gallate in Lung Cancer Cells[J].ANTICANCER RESEARCH.2009,29(6):2025-2030.
APA:
Gao, Zhi,Xu, Zhidong,Hung, Ming-Szu,Lin, Yu-Ching,Wang, Tianyou...&You, Liang.(2009).Promoter Demethylation of WIF-1 by Epigallocatechin-3-gallate in Lung Cancer Cells.ANTICANCER RESEARCH,29,(6)
MLA:
Gao, Zhi,et al."Promoter Demethylation of WIF-1 by Epigallocatechin-3-gallate in Lung Cancer Cells".ANTICANCER RESEARCH 29..6(2009):2025-2030