Transformed immortalized gastric epithelial cells by virulence factor CagA of Helicobacter pylori through Erk mitogen-activated protein kinase pathway.
CagA of Helicobacter pylori is a protein that has been closely associated with gastric cancer and that can intervene with signal pathways in cells. Its precise relationship with the occurrence of gastric cancer, however, remains unclear. The purpose of this study is to investigate whether CagA can promote transformation of normal gastric epithelial cells and to consider via what mechanisms CagA may exert its effects. Transformed colonies were merged in soft-agarose medium after immortalized gastric epithelial cells were transfected with recombinant pLHCX retrovirus with cagA and/or dimethylhydrazine. The number of transformed colonies in the group containing cagA/pLHCX retrovirus, combined with a subthreshold dose of dimethylhydrazine, was more than that for cagA/pLHCX retrovirus or dimethylhydrazine at a subthreshold dose alone. For cagA-transfected cells, only IQGAP-2, R-Ras and B-Raf of the Ras/mitogen-activated protein kinase signal pathway were markedly increased, and the activity of extracellular signal-regulated kinase 1/2 (Erk1/2) kinase was significantly higher than that in dimethylhydrazine-transformed cells or control cells. However, no evidence of alteration of any other molecules of the Ras superfamily was observed in cagA-transfected cells. These findings suggest that CagA can transform gastric epithelial cells through activation of the Erk1/2 pathway; this mechanism may, however, be independent of Ras activation.
Zhu
Yongliang
Y
Gastroenterological Department, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Zhong
Xian
X
Zheng
Shu
S
Du
Qin
Q
Xu
Weizhen
W
D002460:Cell Line; D017931:DNA Primers; D004261:DNA Replication; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014774:Virulence
D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases