Activation of NF-kappa B and AP-1 Mediates Hyperproliferation by Inducing beta-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells

作者：Byun Eunyoung; Park Bohye; Lim Joo Weon; Kim Hyeyoung^*

来源：Yonsei Medical Journal, 2016, 57(3): 647-651.

DOI：10.3349/ymj.2016.57.3.647

• Helicobacter pylori
• NF-kappa B
• AP-1
• oncogenes
• hyperproliferation

Purpose: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as beta-catenin and c-myc. Even though transcription factors NF-kappa B and AP-1 are activated in H. pylori-infected cells, whether NF-kappa B or AP-1 regulates the expression of beta-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-kappa B and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells.
Materials and Methods: Gastric epithelial AGS cells were transiently transfected with mutant genes for I kappa B alpha (MAD3) and c-Jun (TAM67) or treated with a specific NF-kappa B inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-kappa B or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori.
Results: H. pylori induced activation of NF-kappa B and AP-1, cell proliferation, and expression of oncogenes (beta-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-kappa B and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells.
Conclusion: H. pylori-induced activation of NF-kappa B and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.

• 出版日期2016-5