Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells.
10.3349/ymj.2016.57.3.647
- Author:
Eunyoung BYUN
1
;
Bohye PARK
;
Joo Weon LIM
;
Hyeyoung KIM
Author Information
1. Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea. kim626@yonsei.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Helicobacter pylori;
NF-κB;
AP-1;
oncogenes;
hyperproliferation
- MeSH:
Blotting, Western;
Caffeic Acids;
Cell Line, Tumor;
Cell Proliferation;
DNA, Bacterial/analysis/genetics;
DNA-Binding Proteins/*metabolism;
Epithelial Cells/*metabolism;
Gastric Mucosa/*metabolism/pathology;
Gastritis/pathology;
Gene Expression Regulation, Bacterial;
Helicobacter Infections/metabolism/pathology/physiopathology;
Helicobacter pylori/pathogenicity/physiology;
Humans;
NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism;
Peptide Fragments;
Phenylethyl Alcohol/analogs & derivatives;
Proto-Oncogene Proteins c-jun;
Repressor Proteins;
Transcription Factor AP-1/*biosynthesis;
Transcription Factors/*metabolism;
beta Catenin/*metabolism
- From:Yonsei Medical Journal
2016;57(3):647-651
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-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-κB 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 IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB 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-κB and AP-1, cell proliferation, and expression of oncogenes (β-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-κB 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-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
