Yonsei Med J.  2016 May;57(3):647-651. 10.3349/ymj.2016.57.3.647.

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

Affiliations
  • 1Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea. kim626@yonsei.ac.kr
  • 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.

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.

Keyword

Helicobacter pylori; NF-κB; AP-1; oncogenes; hyperproliferation

MeSH Terms

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
Caffeic Acids
DNA, Bacterial
DNA-Binding Proteins
NF-kappa B
Peptide Fragments
Phenylethyl Alcohol
Proto-Oncogene Proteins c-jun
Repressor Proteins
Transcription Factor AP-1
Transcription Factors
beta Catenin
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