Helicobacter pylori inhibits gastric cell cycle progression.
Helicobacter pylori infection of the gastric mucosa is associated with changes in gastric epithelial cell proliferation. In vitro studies have shown that exposure to H. pylori inhibits proliferation of gastric cells. This study sought to investigate the cell cycle progression of gastric epithelial cell lines in the presence and absence of H. pylori. Unsynchronized and synchronized gastric epithelial cell lines AGS and KatoIII were exposed to H. pylori over a 24-h period. Cell cycle progression was determined by flow cytometry using propidium iodide (PI), and by analysis of cyclin E, p21, and p53 protein expression using Western blots. In the absence of H. pylori 40, 45, and 15% of unsynchronized AGS cells were in G(0)-G(1), S, and G(2)-M phases, respectively, by flow cytometry analysis. When AGS cells were cultured in the presence of H. pylori, the S phase decreased 10% and the G(0)-G(1) phase increased 17% after 24 h compared with the controls. KatoIII cells, which have a deleted p53 gene, showed little or no response to H. pylori. When G1/S synchronized AGS cells were incubated with media containing H. pylori, the G(1) phase increased significantly (25%, P < 0.05) compared with controls after 24 h. In contrast, the control cells were able to pass through S phase. The inhibitory effects of H. pylori on the cell cycle of AGS cells were associated with a significant increase in p53 and p21 expression after 24 h. The expression of cyclin E was downregulated in AGS cells following exposure of AGS cells to H. pylori for 24 h. This study shows that H. pylori-induced growth inhibition in vitro is predominantly at the G(0)-G(1) checkpoint. Our results suggest that p53 may be important in H. pylori-induced cell cycle arrest. These results support a role for cyclin-dependent kinase inhibitors in the G(1) cell cycle arrest exerted by H. pylori and its involvement in changing the regulatory proteins, p53, p21, and cyclin E in the cell cycle.
Ahmed
A
A
Gastroenterology Division, Howard University, Washington DC, 20059, USA.
Smoot
D
D
Littleton
G
G
Tackey
R
R
Walters
C S
CS
Kashanchi
F
F
Allen
C R
CR
Ashktorab
H
H
D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004396:Coloring Agents; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism*; D015151:Immunoblotting; D011419:Propidium; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D004396:Coloring Agents; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; C080866:cagA protein, Helicobacter pylori; D011419:Propidium