title: Role of Helicobacter pylori and p53 in regulation of gastric epithelial cell cycle phase progression.
abstract: H. pylori disrupts gastric mucosal homeostasis by altering gastric epithelial cell cycle distribution, and this may contribute to the diverse disease outcomes associated with this infection. The effect of H. pylori on gastric epithelial cells and the role of p53 were assessed in this study by incubating H. pylori strains with gastric epithelial cells. During a 72-hr coincubation, H. pylori induced a time- and dose-dependent inhibition of cell growth and induction of apoptosis. However, at low inocula, H. pylori stimulates cell DNA synthesis compared to untreated controls. Although there was no difference in the induction of AGS cell line apoptosis and cell proliferation between cells exposed to cagA+/vacA+ and cagA-/vacA- strains, an interstrain variation on H. pylori-induced cell cycle events was noted. Serum starvation enhanced the sensitivity of gastric epithelial cells to H. pylori-induced apoptosis. H. pylori induced apoptosis in all the cell lines regardless of their p53 status, but cells with wild-type p53 had higher apoptosis rates. Therefore, bacterial density, diversity, local nutrient levels, and host cell p53 status may contribute to the regulation of H. pylori-induced cell cycle events.
authors.affiliation: Digestive Diseases Research Centre, St Bartholomew's, London, UK.
authors.forename: Zun-Wu
authors.initials: ZW
authors.lastname: Zhang
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Patchett
authors.forename: Michael J G
authors.initials: MJ
authors.lastname: Farthing
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology*; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology*; D016480:Helicobacter pylori / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53