title: IL-1β-stimulated urokinase plasminogen activator expression through NF-κB in gastric cancer after HGF treatment.
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.
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Sung Ae
authors.initials: SA
authors.lastname: Koh
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Gastro-Enterology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Jang
authors.affiliation: Department of Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000473:pathology*; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017228:Hepatocyte Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D014568:Urokinase-Type Plasminogen Activator