cDNA microarray analysis of Helicobacter pylori-mediated alteration of gene expression in gastric cancer cells

Biochem Biophys Res Commun. 2001 Jun 8;284(2):443-9. doi: 10.1006/bbrc.2001.5006.

Abstract

Helicobacter pylori infection stimulates several intracellular signaling pathways and is accompanied by increased gene expression in gastric epithelial cells. High-density cDNA microarray was used to characterize the mRNA expression profile of genes in human gastric cancer cells (MKN45, AGS) cocultured with H. pylori. Coculture with cag pathogenicity island (PAI)-positive H. pylori (wild-type) significantly up-regulated mRNA expression in 8 of 2304 genes tested. In 6 (interleukin-8, I(kappaB)alpha, A20, ERF-1, keratin K7, glutathione peroxidase) of the 8 genes, up-regulation was confirmed by RT-PCR. In coculture with isogenic cagE-negative mutant ((Delta)cagE), which encodes a type IV secretion system with other genes in the cag PAI, no significant up-regulation was found. We further analyzed the role of A20. Transfection of expression vector encoding A20 resulted in an inhibition of H. pylori-mediated NF-kappaB activation, indicating that H. pylori-mediated A20 expression could be a negative regulator of NF-kappaB activation. Taken together, these results indicate the importance of microarray technology as a tool for analyzing the complex interplay between H. pylori and the host.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / microbiology
  • Adenocarcinoma / pathology
  • Antigens, Bacterial*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / pharmacology
  • Coculture Techniques
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Helicobacter Infections / genetics
  • Helicobacter Infections / metabolism
  • Helicobacter pylori / genetics
  • Helicobacter pylori / growth & development
  • Helicobacter pylori / metabolism*
  • Humans
  • I-kappa B Proteins*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor alpha-Induced Protein 3

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nuclear Proteins
  • PicB protein, Helicobacter pylori
  • Proteins
  • RNA, Messenger
  • Transcription Factors
  • cagA protein, Helicobacter pylori
  • NF-KappaB Inhibitor alpha
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3