H pylori stimulates proliferation of gastric cancer cells through activating mitogen-activated protein kinase cascade.
OBJECTIVE
To explore the mechanism by which H pylori causes activation of gastric epithelial cells.


METHODS
A VacA (+) and CagA (+) standard H pylori line NCTC 11637 and a human gastric adenocarcinoma derived gastric epithelial cell line BGC-823 were applied in the study. MTT assay and (3)H-TdR incorporation test were used to detect the proliferation of BGC-823 cells and Western blotting was used to detect the activity and existence of related proteins.


RESULTS
Incubation with H pylori extract increased the proliferation of gastric epithelial cells, reflected by both live cell number and DNA synthesis rate. The activity of extracellular signal-regulated protein kinase (ERK) signal transduction cascade increased within 20 min after incubation with H pylori extract and appeared to be a sustained event. MAPK/ERK kinase (MEK) inhibitor PD98059 abolished the action of H pylori extract on both ERK activity and cell proliferation. Incubation with H pylori extract increased c-Fos expression and SRE-dependent gene expression. H pylori extract caused phosphorylation of several proteins including a protein with molecular size of 97.4 kDa and tyrosine kinase inhibitor genistein inhibited the activation of ERK and the proliferation of cells caused by H pylori extract.


CONCLUSIONS
Biologically active elements in H pylori extract cause proliferation of gastric epithelial cells through activating tyrosine kinase and ERK signal transduction cascade.
Chen
Yong-Chang
YC
School of Medicine, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China. ycchen54@ujs.edu.cn
Wang
Ying
Y
Li
Jing-Yan
JY
Xu
Wen-Rong
WR
Zhang
You-Li
YL
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D019833:Genistein / Q000494:pharmacology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D016760:Proto-Oncogene Proteins c-fos; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one