title: Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Byun
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Bohye
authors.initials: B
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.|Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea. kim626@yonsei.ac.kr.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D002109:Caffeic Acids; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005756:Gastritis / Q000473:pathology; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D010446:Peptide Fragments; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D002109:Caffeic Acids; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C543450:MXD3 protein, human; C116115:MYCBP protein, human; D016328:NF-kappa B; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; C439528:TAM67 peptide; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051176:beta Catenin; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: AP-1; Helicobacter pylori; NF-κB; hyperproliferation; oncogenes