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Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells

Authors
 Mi H. Kim  ;  Hyung S. Yoo  ;  Young D. Jung  ;  Bong W. Ahn  ;  Boo A. Shin  ;  Kyung K. Kim  ;  Hyeong R. Kim  ;  Min K. Baek  ;  Hee J. Jang 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Vol.19(4) : 689-697, 2007 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 
ISSN
 1107-3756 
Issue Date
2007
MeSH
Acetylcysteine/pharmacology ; Carcinoma/enzymology ; Carcinoma/microbiology ; Carcinoma/pathology* ; Free Radical Scavengers/pharmacology ; Helicobacter pylori* ; Humans ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Nitriles/pharmacology ; Reactive Oxygen Species/metabolism* ; Receptors, Cell Surface/agonists* ; Receptors, Urokinase Plasminogen Activator ; Signal Transduction ; Stomach Neoplasms/enzymology ; Stomach Neoplasms/microbiology ; Stomach Neoplasms/pathology* ; Sulfones/pharmacology ; Tumor Cells, Cultured
Keywords
helicobacter pylori ; urokinase plasminogen activator receptor ; reactive oxygen species ; NF-κB ; gastric cancer
Abstract
The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H2O2 content, as determined using H2O2-sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H2O2 and uPAR expression. In addition, exogenous H2O2 was found to increase uPAR mRNA expression and its promoter activity. Site-directed mutagenesis of the potential NF-kappaB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-kappaB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutated-type NF-kappaB-inducing kinase and I-kappaB, and a specific inhibitor of NF-kappaB (BAY11-7082) decreased the H. pylori-induced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-kappaB. With the aid of NAC and H2O2, it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-kappaB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-kappaB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells.
Full Text
http://www.spandidos-publications.com/ijmm/19/4/689
DOI
10.3892/ijmm.19.4.689
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96172
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