Transcription factor Egr-1 is essential for maximal matrix metalloproteinase-9 transcription by tumor necrosis factor alpha

Soon Young Shin, Ji Ho Kim, Andrew Baker, Yoongho Lim, Young Han Lee

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Matrix metalloproteinase-9 (MMP-9) is involved in a wide range of normal and pathologic conditions, including inflammation, tissue repair, tumor invasion, and metastasis. Tumor necrosis factor alpha (TNFalpha) is a major proinflammatory cytokine that plays crucial roles in tumor progression, including tumor invasion and metastasis in the tumor microenvironment. Egr-1 is a member of the zinc-finger transcription factor family induced by diverse stimuli, including TNFalpha. However, the role of Egr-1 in MMP-9 expression was previously unknown. This study shows that Egr-1 directly binds to the MMP-9 promoter and plays an essential role for TNFalpha induction of MMP-9 transcription. Furthermore, Egr-1 together with NF-kappaB can synergistically activate both basal and TNFalpha-induced MMP-9 promoter activities in the presence of p300. We found that Egr-1 mediates extracellular signal-regulated kinase and c-jun NH(2)-terminal kinase mitogen-activated protein kinase-dependent MMP-9 transcription on TNFalpha stimulation. The requirement for Egr-1 in MMP-9 expression is further supported by the fact that HeLa cells expressing Egr-1 siRNA and Egr-1-null mouse embryonic fibroblasts were refractory to TNFalpha-induced MMP-9 expression. This report establishes that Egr-1 is essential for MMP-9 transcription in response to TNFalpha within the tumor microenvironment.

Original languageEnglish
Pages (from-to)507-19
Number of pages13
JournalMolecular Cancer Research
Issue number4
Publication statusPublished - Apr 2010

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Cells, Cultured
  • Early Growth Response Protein 1
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Small Interfering
  • Transcriptional Activation
  • Tumor Necrosis Factor-alpha
  • p300-CBP Transcription Factors


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