Abstract
Particular Helicobacter pylori genotypes differentially induce epithelial cell proliferation, but the mechanisms are not characterized. We explored the effect of H. pylori CagA on expression of cyclin D1, an important cell cycle regulator. H. pylori-induced cell survival and cyclin D1 expression were attenuated in a cagA mutant. AP1 and cAMP response element (CRE), but not NF-kappaB, were involved in the induced cyclin D1 expression. Diminished mitogen-activated protein kinase (MAPK) activation, especially involving p38, with downstream effects on AP1 and CRE activation, was observed for the cagA mutant. In total, these data show that cagA+ H. pylori strains are enhanced in their ability to activate MAPKs and downstream transcription factors, increasing cyclin D1 expression, G1-S phase progression, and host cell survival, explaining both the preferential survival of affected host cells, and the enhanced oncogenesis by these bacteria.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Bacterial / genetics*
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Bacterial Proteins / genetics*
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Blotting, Western
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Cell Cycle / genetics*
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Cell Cycle / physiology
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Cell Line, Tumor
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Cell Survival / genetics
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Cell Survival / physiology
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Chromatin Immunoprecipitation
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Cyclin D1 / genetics*
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Cyclin D1 / metabolism
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Flavonoids / pharmacology
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Flow Cytometry
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Gene Expression / drug effects
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Gene Expression / genetics
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Helicobacter Infections / genetics*
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Helicobacter Infections / metabolism
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Helicobacter Infections / microbiology
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Helicobacter pylori / genetics*
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Helicobacter pylori / growth & development
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Humans
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Imidazoles / pharmacology
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Luciferases / genetics
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Luciferases / metabolism
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Mutation / genetics
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NF-kappa B / metabolism
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Phosphorylation
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Protein Binding
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Pyridines / pharmacology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Transcription Factor AP-1 / metabolism
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Transcription Factors / metabolism
Substances
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Antigens, Bacterial
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Bacterial Proteins
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Flavonoids
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Imidazoles
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NF-kappa B
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Pyridines
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Recombinant Fusion Proteins
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Transcription Factor AP-1
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Transcription Factors
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cagA protein, Helicobacter pylori
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Cyclin D1
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Luciferases
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Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one