Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells.

摘要: Cyclooxygenase (COX)-2, the inducible form of rate-limiting enzyme for prostaglandin synthesis, is up-regulated in gastrointestinal cancers and a key mediator epithelial cell growth. Helicobacter pylori causally linked to gastric cancer. In H. gastritis, COX-2 expression localizes subepithelial region, with variable levels epithelium. contrast, cancer, strongly predominates epithelium, suggesting that transition consistent overexpression may be critical molecular event carcinogenesis. Because aberrant promoter methylation inhibits variety genes cancers, we sought determine whether could regulate response cells. We assessed status six lines. all four lines exhibited basal significant increase pylori, was unmethylated, whereas two did not express COX-2, methylated. Treatment COX-2-methylated cells demethylating agent 5-azacytidine had modest effect on expression, but when 5-azacytidine-treated were subsequently stimulated there significant, 5–10-fold enhancement both mRNA protein release product, E2. COX-2-expressing unmethylated at promoter, no pylori-stimulated expression. These findings suggest loss facilitate promote carcinogenesis associated infection.