Altered expression of Skp2, c-Myc and p27 proteins but not mRNA after H. pylori eradication in chronic gastritis.
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 (mean+/-s.e.m. 37+/-2.4% pre-eradication vs 55+/-2.8% post-eradication; P<0.001), while Skp2 and c-Myc protein-expressing cells were lower (Skp2: 35+/-3.8 vs 23+/-2.6%, P=0.009; c-Myc: 47+/-3.6 vs 30+/-3.8%, 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.
Kim
Sung S
SS
Department of Medicine, Rhode Island Hospital/Brown University, Providence, RI 02903, USA.
Meitner
Patricia
P
Konkin
Tamako A
TA
Cho
Young S
YS
Resnick
Murray B
MB
Moss
Steven F
SF
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D002908:Chronic Disease; D017291:Clarithromycin / Q000627:therapeutic use; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005756:Gastritis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D016209:Interleukin-8; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D044786:S-Phase Kinase-Associated Proteins; D064747:Lansoprazole; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole