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

Shin, S.Y., Kim, J.H., Baker, A.H., Lim, Y. and Lee, Y.H. (2010) Transcription factor Egr-1 is essential for maximal matrix metalloproteinase-9 transcription by tumor necrosis factor α. Molecular Cancer Research, 8(4), pp. 507-519. (doi: 10.1158/1541-7786.MCR-09-0454) (PMID:20332214)

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Abstract

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 α (TNFα) 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 TNFα. 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 TNFα induction of MMP-9 transcription. Furthermore, Egr-1 together with NF-κB can synergistically activate both basal and TNFα-induced MMP-9 promoter activities in the presence of p300. We found that Egr-1 mediates extracellular signal–regulated kinase and c-jun NH2-terminal kinase mitogen-activated protein kinase–dependent MMP-9 transcription on TNFα 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 TNFα-induced MMP-9 expression. This report establishes that Egr-1 is essential for MMP-9 transcription in response to TNFα within the tumor microenvironment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew
Authors: Shin, S.Y., Kim, J.H., Baker, A.H., Lim, Y., and Lee, Y.H.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Molecular Cancer Research
ISSN:1541-7786
ISSN (Online):1557-3125
Published Online:23 March 2010

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