Abstract 2592: Helicobacter pylori induces phosphorylation of STAT3 Tyr705 and Ser727 in human gastric epithelial cells

Helicobacter pylroi (H. pylori) infection has been considered to be one of the high risk factors of gastritis and gastric cancer, but its pathogenic implication is still poorly understood. Recent studies indicate that constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated carcinogenesis. In our previous study, we found that the phosphorylation of STAT3 at Tyr705 was increased in H. pylori plus high salt diet-induced gastritis in a mouse model. The similar results were observed in human gastric AGS cells co-cultured with H. pylori. Interestingly, H. pylori induced phosphorylation of STAT3 at not only Tyr705 but also Ser727. However, the phosphorylation of two residues exhibited different profiles in human gastric epithelial cells upon H. pylori treatment. The phosphor-Tyr705 increased at early time of H. pylori infection and then decreased immediately, but phosphor-Ser727 increased thereafter which was first discovered in our present study. Phosphorylation of STAT3 is an essential event for inducing the expression of anti-apoptotic/survival proteins, such as Bcl-XL, BcL-2, survivin and c-Myc which contribute to gastric carcinogenesis. Levels of all these proteins were elevated in H. pylori-infected AGS cells. In conclusion, H. pylori induces phosphorylation of STAT3 at both Tyr705 and Ser727 residues. The role of phospohorylation of STAT3 at the Serine 727 residue in H. pylori-induced gastritis and gastric cancer is under investigation. Citation Format: Juan-Yu Piao, Hee-Geum Lee, Hyeon-Geum Ji, Hyeong-Joon Han, Hoang Kieu Chi Ngo, Do-Hee Kim, Su-Jung Kim, Sung-Young Lee, Young-Joon Surh. Helicobacter pylori induces phosphorylation of STAT3 Tyr705 and Ser727 in human gastric epithelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2592. doi:10.1158/1538-7445.AM2013-2592