|Title:||Comparative immunoproteomics of idenfication and characterization of virulence factors from helicobacter pylori related to gastric cancer||Authors:||LU-PING CHOW
|Issue Date:||2006||Journal Volume:||5||Journal Issue:||8||Start page/Pages:||1484-1496||Source:||Molecular and Cellular Proteomics||Abstract:||
Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase α subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2. Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27Kip1. We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation. ? 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
|DOI:||10.1074/mcp.M600111-MCP200||metadata.dc.subject.other:||acid; bacterial antigen; chaperonin; cyclin D1; cyclin dependent kinase inhibitor 1B; cyclooxygenase 2; DNA directed DNA polymerase alpha; glycine; granulocyte colony stimulating factor; hybrid protein; interleukin 1beta; interleukin 6; interleukin 8; membrane protein; methionine adenosyltransferase; prostaglandin E2; protein c fos; protein c jun; synthetase; threonine; tumor necrosis factor alpha; virulence factor; bacterial antigen; chaperonin; cyclooxygenase 2; cytokine; membrane protein; prostaglandin E2; proteome; PTGS2 protein, human; virulence factor; antigen detection; article; blood sampling; carcinogenesis; cell proliferation; confidence interval; controlled study; cytokine production; down regulation; duodenum ulcer; epithelium cell; female; gastritis; gene identification; Helicobacter pylori; human; human cell; human tissue; immunoblotting; incubation time; inflammation; major clinical study; male; mass spectrometry; peripheral blood mononuclear cell; priority journal; protein expression; protein function; proteomics; risk assessment; stomach cancer; stomach epithelium; upregulation; biosynthesis; cell culture; comparative study; cytology; duodenum ulcer; gastritis; gene expression regulation; Helicobacter infection; immunology; metabolism; microbiology; mononuclear cell; stomach mucosa; stomach tumor; Helicobacter pylori; Antigens, Bacterial; Cells, Cultured; Cyclooxygenase 2; Cytokines; Dinoprostone; Duodenal Ulcer; Gastric Mucosa; Gastritis; Gene Expression Regulation; GroES Protein; Helicobacter Infections; Helicobacter pylori; Humans; Leukocytes, Mononuclear; Membrane Proteins; Proteome; Stomach Neoplasms; Virulence Factors
|Appears in Collections:||醫學系|
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