Urokinase plasminogen activator receptor is upregulated by Helicobacter pylori in human gastric cancer AGS cells via ERK, JNK, and AP-1.
The gastric pathogen Helicobacter pylori (H. pylori) is suggested to be associated with gastric cancer progression. In this study, we investigated the effect of H. pylori on urokinase plasminogen activator receptor (uPAR) expression which has been known to correlate closely with gastric cancer invasion. H. pylori induced the uPAR expression in a time- and concentration-dependent manner. Specific inhibitors and inactive mutants of MEK-1 and JNK were found to suppress the H. pylori-induced uPAR expression and the uPAR promoter activity. Electrophoretic mobility shift assay and transient transfection study using an AP-1 decoy oligonucleotide confirmed that the activation of AP-1 is involved in the H. pylori-induced uPAR upregulation. The AGS cells treated with H. pylori showed a remarkably enhanced invasiveness, and this effect was partially abrogated by uPAR-neutralizing antibodies. These results suggest that H. pylori induces uPAR expression via Erk-1/2, JNK, and AP-1 signaling pathways and, in turn, stimulates the cell invasiveness in human gastric cancer AGS cells.
Kim
Mi H
MH
Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Kwangju 501-190, Republic of Korea.
Yoo
Hyung S
HS
Chang
Hee J
HJ
Hong
Min H
MH
Kim
Ho D
HD
Chung
Ik J
IJ
Shin
Boo A
BA
Cho
Myung J
MJ
Ahn
Bong W
BW
Jung
Young D
YD
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator