T1628 Genome-Wide Hypomethylation Associated with Regional Hypermethylation in H. pylori-Related Enlarged Fold Gastritis

Abstract

G A A b st ra ct s STAT3mRNA and protein in a dose dependent manner without alteration in cellular phophoSTAT3 level. The concentration of VacA was appropriated with 120nM for the following experiments. Relative mRNA expression levels of Bcl-2 and Bcl-XL were significantly decreased, and their cellular protein levels were substantially decreased thereafter. Knockdown of STAT3, Bcl-2 and Bcl-XL but not Mcl-1 by siRNA induced significant apoptosis in AZ-521 cells, which augmented VacA-induced apoptosis. The reduction in STAT3, Bcl2 and Bcl-XL and resultant apoptosis were affected by a JNK inhibitor I but not bafilomycin A1, a vacuolating inhibitor. Conclusion: VacA causes reduction of cellular levels of STAT3 and its downstream transcribed molecules, Bcl-2 and Bcl-XL, leading to apoptosis. This novel action of VacA is at least in part dependent on JNK pathway, providing new insights on the molecular mechanisms of VacA-induced apoptosis.