Effects of H-pylori infection of gastric epithelial cells on cell cycle control

Chronic infection of the gastric mucosa by the bacterium H. pylori results in an intense inflammatory response which can last for decades. An associat ed host response is a chronic hyperproliferative state, in which there is i ncreased cell turnover and also increased apoptosis of the gastric epitheli al cells. Recent studies have also demonstrated abnormalities in the expres sion of cell cycle control proteins. This review describes these events, em phasizing recent studies on the effects of H. pylori infection on cell cycl e progression and the expression of cell cycle regulatory proteins. The sys tems that have been studied include in vivo studies in humans and in experi mental animals, and in vitro studies in which gastric epithelial cells were co-cultivated with H. pylori. The earliest event following H. pylori's int eraction with epithelial cells appears to be growth inhibition and apoptosi s. The hyperproliferative response observed in the gastric mucosa is second ary to this initial insult and is associated with increased expression of c yclin D1, the cyclin dependent kinase inhibitor p16(ink4a) and of p53 and d ecreased expression of the cyclin dependent kinase inhibitor p27(kip1). Dys regulation of the hyperproliferative response may, ultimately, be responsib le for the ability of H. pylori to enhance the development of gastric cance r.