The genome-wide expression profile of gastric epithelial cells infected by naturally occurring cagA isogenic strains of Helicobacter pylori

Environ Toxicol Pharmacol. 2011 Nov;32(3):382-9. doi: 10.1016/j.etap.2011.08.006. Epub 2011 Aug 16.

Abstract

Helicobacter pylori (H. pylori) is associated with the development of gastric adenocarcinoma and lymphoma. However, the mechanisms through which H. pylori induces gastric mucosal lesions are not well defined. This study was conducted to evaluate the effect of the oncoprotein CagA on gastric cancer cells using whole-genome expression arrays. Human gastric epithelial (AGS) cells were incubated with CagA-positive H. pylori strains (147C (phosphorylated CagA) or 147A (dephosphorylated CagA)), and total protein and RNA were collected. The effects of phosphorylated and unphosphorylated CagA on AGS cells were then evaluated using Western blotting and microarray analysis. The expression levels of the genome profiles of AGS cells infected with 147A were compared with those of AGS cells infected with 147C. The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated via quantitative real-time PCR. Up- and down-regulated genes mainly included epithelial mesenchymal transition (EMT)-related genes. The results of the microarray analysis revealed that phosphorylated and unphosphorylated CagA may affect EMT in part through gene expression. This suggests that the intracellularly translocated CagA may be involved in EMT, resulting in differential expression of genes independent on the phosphorylation status of CagA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / metabolism*
  • Blotting, Western
  • Cell Line, Tumor
  • Epithelial Cells / microbiology*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genome, Human
  • Helicobacter Infections / genetics
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / genetics
  • Helicobacter pylori / metabolism
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Mesoderm
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Protein Transport
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / pathology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • cagA protein, Helicobacter pylori