title: Down-modulation of Bis reduces the invasive ability of glioma cells induced by TPA, through NF-κB mediated activation of MMP-9.
abstract: Bcl-2 interacting cell death suppressor (Bis) has been shown to have anti-apoptotic and anti-stress functions. Recently, increased Bis expression was reported to correlate with glioma aggressiveness. Here, we investigated the effect of Bis knockdown on the acquisition of the invasive phenotype of A172 glioma cells, induced by 12-O-Tetradecanoylphorbol-3-acetate (TPA), using a Transwell assay. Bis knockdown resulted in a significant decrease in the migration and invasion of A172 cells. Furthermore, Bis knockdown notably decreased TPA-induced matrix metalloproteinase-9 (MMP-9) activity and mRNA expression, as measured by zymography and quantitative real time PCR, respectively. A luciferase reporter assay indicated that Bis suppression significantly down-regulated NF-κB-driven transcription. Finally, we demonstrated that the rapid phosphorylation and subsequent degradation of IκB-α induced by TPA was remarkably delayed by Bis knockdown. These results suggest that Bis regulates the invasive ability of glioma cells elicited by TPA, by modulating NF-κB activation, and subsequent induction of MMP-9 mRNA.
authors.affiliation: Department of Biochemistry, Cancer Research Institute, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Mei Nu
authors.initials: MN
authors.lastname: Cui
authors.affiliation: Department of Biochemistry, Cancer Research Institute, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, Cancer Research Institute, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Cancer Evolution Research Center, Catholic High-Performance Cell Therapy Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Il-Hoan
authors.initials: IH
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, Cancer Research Institute, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate