cDNA Microarray Analysis of Helicobacter pylori-Mediated Alteration of Gene Expression in Gastric Cancer Cells

• Published in: Biochemical and biophysical research communications 2001-06, Vol.284 (2), p.443-449
• Main Authors: Maeda, Shin, Otsuka, Motoyuki, Hirata, Yoshihiro, Mitsuno, Yuzo, Yoshida, Haruhiko, Shiratori, Yasushi, Masuho, Yasuhiko, Muramatsu, Masa-aki, Seki, Naohiko, Omata, Masao
• Format: Article
• Language: English
• Subjects: A20 gene; Adenocarcinoma - metabolism; Adenocarcinoma - microbiology; Adenocarcinoma - pathology; Antigens, Bacterial; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacterial Proteins - pharmacology; cagE gene; Coculture Techniques; DNA microarrays; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; gastric carcinoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Helicobacter Infections - genetics; Helicobacter Infections - metabolism; Helicobacter pylori; 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-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; pathogenicity islands; 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
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.5006

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, IκBα, 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 (ΔcagE), 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-κB activation, indicating that H. pylori-mediated A20 expression could be a negative regulator of NF-κB 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.