title: Regulation of HGF-mediated cell proliferation and invasion through NF-κB, JunB, and MMP-9 cascades in stomach cancer cells.
abstract: Blocking of activator protein-1 activity leads to suppression of growth factor-induced transformation. However, the role of individual components of the Jun family in this process is unclear. Over-expression of JunB has been reported to be associated with neoplastic transformation and regulation of Matrix metalloproteinase-9 (MMP-9) expression. Using cDNA microarray, we found that JunB might be one of target genes up-regulated by hepatocyte growth factor (HGF). Therefore, we tried to investigate the role of JunB in HGF-medicated cell proliferation and cell invasion in human gastric cancer cells, NUGC3 and MKN28. We verified that HGF increased JunB in time and dose-dependent manners. The JunB levels were decreased by the treatment with an NF-κB inhibitor, pyrrolidine dithiocarbamate. Down-regulation of JunB by transfecting cells with JunB-short hairpin RNAs (shRNA) inhibited MMP-9 up-regulation induced by HGF. Furthermore, transfection with JunB-shRNA repressed HGF-mediated increases in cell proliferation and cell invasion. These data suggest that JunB might be regulated through an NF-κB pathway and up-regulation of JunB induced by HGF might play an important role in the regulation of cell proliferation and cell invasion through MMP-9 expression. In conclusion, these results may contribute to the JunB-associated malignant phenotype of gastric cancers by regulating MMP-9, and serve as a novel therapeutic target for stomach cancer therapy in the future.
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Republic of Korea. lkhee@med.yu.ac.kr
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D009361:Neoplasm Invasiveness; D011725:Pyridines / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000502:physiology*
chemical_list: D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; D018808:Transcription Factor AP-1; D017228:Hepatocyte Growth Factor; D020780:Matrix Metalloproteinase 9; C093642:SB 203580