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Aberrant methylation frequency of TNFRSF10C promoter in pancreatic cancer cell lines
发布时间:2016-11-28   浏览次数:925

Abstract

BACKGROUND:A growing body of evidence suggests that manytumors are initiated by both epigenetic abnormalities and gene mutations, whichpromote tumor progression. Epigenetic abnormalities include changes in DNAmethylation and in the modification of histones. This study aimed to assess thestatus of methylation in the CpG island (CGI) of the tumor necrosis factorreceptor superfamily member 10c (TNFRSF10C) with combined bisulfite restrictionanalysis (COBRA) and to evaluate its role in the progression of pancreaticcancer (PC).

METHODS:The methylation status of four PC cell lines wasassessed using COBRA and/or bisulfite genomic sequencing (BGS). Changes inmethylation and TNFRSF10C expression in PC cell lines before and aftertreatment with 5-aza-2'-deoxycytidine (5-aza-dC) and/or trichostatin A (TSA)were assessed by BGS and real-time RT-PCR. Apoptosis in the four cell lines wastested by flow cytometry (FCM) and TUNEL assay.

RESULTS:The methylation status of the TNFRSF10C promoterwas assessed in PC cells (BxPC-3: 68.84+/-8.71%; CFPAC-1: 0; PANC-1:96.77+/-4.57%; SW1990: 54.97+/-7.33%) with the COBRA assay, which was confirmedby the results of BGS. After treatment with 5-aza-dC and/or TSA, apoptosis wasinduced in PC cells to different degrees, and the levels of TNFRSF10Ctranscriptional expression in the PC cell lines (except CFPAC-1) increasedmarkedly after 5-aza-dC treatment.

CONCLUSIONS:A high frequency of CGI methylation in theTNFRSF10C promoter results in inactivation of the gene and enhancement of tumorgrowth in most PC cell lines (except CFPAC-1). Inactivation of TNFRSF10C by CGIhypermethylation can play an important role in PC progression and bepotentially useful as a diagnostic marker and a new therapeutic approach forPC.