Helicobacter pylori inhibits the G(1) to S transition in AGS gastric epithelial cells

Infection with the bacterium Helicobacter pylori is associated epidemiologi cally with development of gastric cancer, To better understand the role of H. pylori in carcinogenesis, we examined the effects of H. pylori on cell c ycle-related events in the AGS gastric cancer cell line. During coculture, wild-type, toxigenic, cagA-positive H. pylori induced both apoptosis and in hibition of cell cycle progression at G(1)-S in AGS cells. These effects we re most apparent in AGS cells synchronized by serum-deprivation and then st imulated to progress through the cell cycle by refeeding, An isogenic cagA- negative mutant H. pylori, produced similar effects, In contrast to changes induced by 5-fluorouracil, the inhibition of cell cycle progression from G (1) to S caused by H. pylori was not accompanied by sustained changes in p5 3 or p21(cip1), but was associated with reduced expression of p27(kip1) and inhibition of transcriptional activation of the serum-response element of c-fos, Our results indicate that H. pylori inhibits cell cycle progression at G(1)-S and induces apoptosis, associated with reduced expression of p27( kip1) in AGS gastric cancer cells. In vivo, similar effects as a result of H. pylori infection may lead to potentially deleterious compensatory hyperp roliferation by nonneoplastic gastric epithelial cells.