Du C, Yang P, Zhang G, Hong C, Chen J, Dong X. Effect of Arsenic trioxide on EBV LMP1 mediated E-cadherin silencing in nasopharyngeal carcinoma. Head Neck Oncol. 2012 Sep 9;4(2):55.

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) activates cellular DNA methyltransferases, which results in hypermethylation and thus silencing of E-cadherin. We previously demonstrated that As2O3 can reduce LMP1 expression in human nasopharyngeal carcinoma (NPC) cells in vitro. The purpose of the current study is to determine whether As2O3 can rescue the expression of E-cadherin in NPC cells through repressing LMP1. The stable LMP1 (HNE1-LMP1) and its parental (HNE1) cell lines were treated with various concentration of As2O3for 48 h. The DNA methylation at E-cadheringene promoter of survival cells were investigated by methylation-specific polymerase chain reaction (MSP). The expression levels of E-cadherin mRNA and protein in these cells were analyzed by quantitative RT-PCR and Western blot, respectively.Transwell assay was used to measure the invasive properties of these cells after exposure to As2O3. The characteristic hypermethylation within silenced E-cadherin was found in HNE1-LMP1 cells when compared to HNE1 cells. As2O3-induced demethylation restored the activity of E-cadherin gene promoter in HNE1-LMP1 cells. E-cadherin mRNA and protein expression levels were upregulated after As2O3 treatment. Accordingly, the invasive ability of HNE1-LMP1 cells also reduced after exposure to As2O3. To conclude, As2O3 could reverse LMP1-mediated methylation and silencing of E-cadherin gene in NPC, restore the gene’s promoter activity and expression, and indicate a po...
Source: Head and Neck Oncology - Category: Cancer & Oncology Source Type: research