IL-1 beta-stimulated urokinase plasminogen activator expression through NF-kappa B in gastric cancer after HGF treatment

Title
IL-1 beta-stimulated urokinase plasminogen activator expression through NF-kappa B in gastric cancer after HGF treatment
Author(s)
이경희최은영고성애김민경장병익김상운김재룡
Keywords
HELICOBACTER-PYLORI INFECTION; CARCINOMA CELLS; INFLAMMATORY CYTOKINES; GENE-EXPRESSION; LUNG-CANCER; INTERLEUKIN-1-BETA; SYSTEM; TUMORIGENESIS; INVASIVENESS; ANGIOGENESIS
Issue Date
201405
Publisher
SPANDIDOS PUBL LTD
Citation
ONCOLOGY REPORTS, v.31, no.5, pp.2123 - 2130
Abstract
The potential of hepatocyte growth factor (HGF) to regulate the expression of urokinase plasminogen activator (uPA) in a gastric cancer cell is not widely acknowledged. To identify the genes associated with the plasminogen activator proteolytic axis by HGF, we used cDNA microarray technology and selected genes upregulated or downregulated in two gastric cell lines (NUGC-3 and MKN-28). First, IL-1 beta RNA and protein were confirmed to be upregulated. Then, we investigated the effect of IL-1 beta induced by HGF on the uPA system, facilitating the migration and invasion of cancer cells in the metastatic process. The role for IL-1 beta in HGF-induced upregulation of uPA was determined by knockdown of IL-1 beta with IL-1 beta shRNA and a chromatin immune precipitation assay. The levels of IL-1 beta and uPA were upregulated in cells treated with HGF in a dose-dependent manner. HGF-induced upregulation of uPA was suppressed by IL-1 beta knockdown. HGF enhanced the binding activity of NF-kappa B to the uPA promoter in control cells, but not in the IL-1 beta shRNA cells. We confirmed the functional role of HGF inactivation of the uPA promoter by a reporter gene assay. Downregulation of IL-1 beta using IL-1 beta shRNA also decreased cell proliferation and in vitro cell invasion. IL-1 beta stimulated uPA expression through ERK and NF-kappa B in gastric cancer, which may therefore be promising targets for gastric cancer therapy.
URI
http://hdl.handle.net/YU.REPOSITORY/32223http://dx.doi.org/10.3892/or.2014.3086
ISSN
1021-335X
Appears in Collections:
의과대학 > 내과학교실 > Articles
의과대학 > 성형외과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
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