Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle

Citation
Rm. Peek et al., Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle, CANCER RES, 59(24), 1999, pp. 6124-6131
Citations number
53
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
59
Issue
24
Year of publication
1999
Pages
6124 - 6131
Database
ISI
SICI code
0008-5472(199912)59:24<6124:HPSGAM>2.0.ZU;2-M
Abstract
Helicobacter pylori cag(+) strains enhance gastric epithelial cell prolifer ation and attenuate apoptosis in vivo, which may partially explain the incr eased risk of gastric cancer associated with these strains. The goals of th is study were to identify specific H. pylori genes that regulate epithelial cell cycle events and determine whether these effects were dependent upon p53-mediated pathways. AGS gastric epithelial cells were cultured alone or in the presence of 21 clinical H. pylori isolates, H. pylori reference stra in 60190, or its isogenic cagA(-), picB(-), vacA(-), or picB(-)/vacA(-) der ivatives. Coculture of H. pylori with AGS cells significantly decreased cel l viability, an effect most prominent with cag(+) strains (P < 0.001 versus cag(-) strains). cag(+) strains significantly increased progression of AGS cells from G(1) into G(2)-M at 6 h and enhanced apoptosis by 72 h. Compare d with the parental 60190 strain, the picB(-) mutant attenuated cell cycle progression at 6 h (P less than or equal to 0.05), and decreased apoptosis with enhanced AGS cell viability at 24 h (P less than or equal to 0.04). Th e vacA(-) mutant decreased apoptosis and enhanced viability at later (48-72 h) time points (P less than or equal to 0.05). Compared with the wild-type strain, the picB(-)/vacA(-) double mutant markedly attenuated apoptosis an d increased cell viability at all time points (P less than or equal to 0.05 ), Furthermore, cocolonization with H. pylori had no significant effect on expression of p53, p21, and MDM2. The diminished AGS cell viability, progre ssion to G(2)-M, and apoptosis associated with cag(+) H. pylori strains wer e dependent upon expression of vacA and genes within the cag pathogenicity island. These results may explain heterogeneity in levels of gastric epithe lial cell proliferation and apoptosis found within H. pylori-colonized muco sa.