1. ¹Department of Medicine, Rhode Island Hospital/Brown University, Providence, RI, USA
2. ²Department of Pathology, Rhode Island Hospital/Brown University, Providence, RI, USA
3. ³Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence: Dr SF Moss, MD, Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, 593 Eddy St, APC 414, Providence, RI 02903, USA. E-mail: Steven_Moss@Brown.edu

Received 15 March 2005; Revised 1 July 2005; Accepted 1 July 2005; Published online 5 August 2005.

Abstract

Helicobacter pylori infection is associated with increased gastric epithelial cell turnover and non-cardia gastric cancer. Cell cycle progression is dependent on the proteasomal degradation of p27, a cyclin-dependent kinase inhibitor and gastric tumor suppressor, following ubiquitination mediated by Skp2. c-Myc is a transcriptional repressor of p27 and also a target of Skp2. In vitro, H. pylori decreases p27 protein post-translationally. We aimed to determine how p27 is regulated by H. pylori in vivo. The effect of eradicating H. pylori on gastric epithelial p27, Skp2, and c-Myc proteins and mRNA was investigated in 22 patients with chronic gastritis, by immunohistochemistry and laser capture microdissection. The percentage of gastric antral epithelial cells expressing p27 protein was significantly higher after eradication of H. pylori (means.e.m. 372.4% pre-eradication vs 552.8% post-eradication; P<0.001), while Skp2 and c-Myc protein-expressing cells were lower (Skp2: 353.8 vs 232.6%, P=0.009; c-Myc: 473.6 vs 303.8%, P<0.001). mRNA expressions of p27, Skp2, and c-Myc (normalized for 18SrRNA) were not changed by H. pylori eradication. H. pylori increases c-Myc and decreases gastric epithelial p27 protein expression in association with increased expression of Skp2, the regulator of p27's ubiquitin ligase complex. H. pylori may influence cell cycle progression and carcinogenesis through post-translational effects on specific gene expression.