Helicobacter pylori inhibits the G1 to S transition in AGS gastric epithelial cells.
Infection with the bacterium Helicobacter pylori is associated epidemiologically with development of gastric cancer. To better understand the role of H. pylori in carcinogenesis, we examined the effects of H. pylori on cell cycle-related events in the AGS gastric cancer cell line. During coculture, wild-type, toxigenic, cagA-positive H. pylori induced both apoptosis and inhibition of cell cycle progression at G1-S in AGS cells. These effects were most apparent in AGS cells synchronized by serum-deprivation and then stimulated 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 G1 to S caused by H. pylori was not accompanied by sustained changes in p53 or p21cip1, but was associated with reduced expression of p27kip1 and inhibition of transcriptional activation of the serum-response element of c-fos. Our results indicate that H. pylori inhibits cell cycle progression at G1-S and induces apoptosis, associated with reduced expression of p27kip1 in AGS gastric cancer cells. In vivo, similar effects as a result of H. pylori infection may lead to potentially deleterious compensatory hyperproliferation by nonneoplastic gastric epithelial cells.
Shirin
H
H
Department of Medicine, St. Luke's-Roosevelt Hospital Center, New York, New York 10025, USA.
Sordillo
E M
EM
Oh
S H
SH
Yamamoto
H
H
Delohery
T
T
Weinstein
I B
IB
Moss
S F
SF
D000942:Antigens, Bacterial; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology; D016193:G1 Phase; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology*; D015964:Gene Expression Regulation, Bacterial; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D016196:S Phase; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D011993:Recombinant Fusion Proteins; C080866:cagA protein, Helicobacter pylori; D005472:Fluorouracil