CpG methylation as a basis of specific loss of normal epithelial cell-specific-1 gene in gastric tumor / 中华消化杂志

ABSTRACT

Objective To investigate the expression of normal epithelial cell-specific-1(NES1) gene in normal gastric epithelial cells and different gastric cancer cell lines and the effects of 5-aza-2-de- oxycytidine(5-aza-dC)on the expression of NES1 gene.Methods Expression of NES1 mRNA in five gastric cancer cell lines(MKN-28,SGC-7901,AGS,MKN-45 and HGC-27)and normal human gastric epithelial cells were detected by real-time PCR.After treatment with 5-aza-dC,a DNA methyltransferase inhibitor,the expression of NES1 mRNA in gastric cancer cell lines was detected by real-time PCR. DNA methylation status of NES1 gene was assayed by methylation-specific PCR(MSP).Results The expression of NES1 mRNA was decreased in all gastric cancer cell lines.A strong correlation between ex on 3 hypermethylation and loss of NES1 mRNA expression in gastric cancer cell lines was noted.5-aza dC treatment of NES1-nonexpressing tumor cell lines resulted in a dose-dependent induction(SGC-7901, MKN-45,MKN-28 and AGS)and increase (HGC-27) of NES1mRNA expression in gastric cancer cells. Conclusions The study suggested that hypermethylation was a responsible factor for tumor-specific loss of NES1 gene expression in gastric cancer cells.Treatment of gastric cancer cell lines with a demethylating agent led to reexpression of NES1 suggesting an important role of hypermethylation in loss of NES1 gene expression.