P-203 - Helicobacter pylori-induced production of reactive oxygen species suppresses the expression of 15-hydroxyprostaglandin dehydrogenase by upregulating DNA methyl transferase

Abstract

Helicobacter pylori (H. pylori) infection causes chronic gastritis and gastric cancer. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme that catalyzes the oxidation of prostaglandin E2 (PGE2) to 15-keto-PGE2. 15-PGDH is speculated as a tumor suppressor as its expression has been frequently down-regulated in diverse human malignancies including gastric cancer. However, the molecular mechanisms underlying 15-PGDH down-regulation in tumorigenesis remain largely unknown. In the present study, we found that the 15-PGDH expression was down-regulated in rat gastric mucosa (RGM)-1 cells infected with H. pylori. H. pylori induced hypermethylation of 15-PGDH promoter. The hypermethylation level of 15-PGDH was higher in the stomach biopsy from H. pylori-infected patients with gastritis than those without H. pylori infection. Notably, H. pylori induced the expression of DNA methyl transferase (DNMT) 1 through generation of reactive oxygen species (ROS). In H. pylori-infected C57BL/6 mice, 15-PGDH expression was reduced while DNMT1 expression was increased in the stomach tissues. In conclusion, H. pylori induces DNA methylation of CpG islands in the 15-PGDH promoter through up-regulation of DNMT1 expression, which is attributable to the generation of ROS.