IL-1β-stimulated urokinase plasminogen activator expression through NF-κB in gastric cancer after HGF treatment

Lee,Kyung Hee; Choi,Eun Young; Koh,Sung Ae; Kim,Min Kyoung; Jang,Byung Ik; Kim,Sang Woon; Kim,Jae-Ryong

doi:10.3892/or.2014.3086

IL-1β-stimulated urokinase plasminogen activator expression through NF-κB in gastric cancer after HGF treatment

Authors:
- Kyung Hee Lee
- Eun Young Choi
- Sung Ae Koh
- Min Kyoung Kim
- Byung Ik Jang
- Sang Woon Kim
- Jae-Ryong Kim
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Affiliations: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea, Department of Gastro-Enterology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea, Department of Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea
Published online on: March 12, 2014 https://doi.org/10.3892/or.2014.3086
Pages: 2123-2130

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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-1β RNA and protein were confirmed to be upregulated. Then, we investigated the effect of IL-1β induced by HGF on the uPA system, facilitating the migration and invasion of cancer cells in the metastatic process. The role for IL-1β in HGF-induced upregulation of uPA was determined by knockdown of IL-1β with IL-1β shRNA and a chromatin immune precipitation assay. The levels of IL-1β and uPA were upregulated in cells treated with HGF in a dose-dependent manner. HGF-induced upregulation of uPA was suppressed by IL-1β knockdown. HGF enhanced the binding activity of NF-κB to the uPA promoter in control cells, but not in the IL-1β shRNA cells. We confirmed the functional role of HGF inactivation of the uPA promoter by a reporter gene assay. Downregulation of IL-1β using IL-1β shRNA also decreased cell proliferation and in vitro cell invasion. IL-1β stimulated uPA expression through ERK and NF-κB in gastric cancer, which may therefore be promising targets for gastric cancer therapy.

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