Transcriptional regulation of the growth-regulated oncogene α gene by early growth response protein-1 in response to tumor necrosis factor α stimulation

Biochim Biophys Acta. 2013 Oct;1829(10):1066-74. doi: 10.1016/j.bbagrm.2013.07.005. Epub 2013 Jul 18.

Abstract

Growth-regulated oncogene α (GROα) plays an important role in a wide range of normal and pathological conditions, including inflammation, angiogenesis, wound healing, tumor invasion, and metastasis. 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 GROα expression was previously unknown. This study shows that Egr-1 directly binds to the GROα promoter and transactivates the GROα gene. Silencing of Egr-1 by expression of Egr-1 siRNA abrogated TNFα-induced GROα transcription. We also found that Egr-1 mediates ERK and JNK MAPK-dependent GROα transcription upon TNFα stimulation. Our findings suggest that Egr-1 may play an important role in tumor development through transactivation of the GROα gene in response to TNFα within the tumor microenvironment.

Keywords: ChIP; Chromatin immunoprecipitation; EBS; EMSA; Egr-1; Egr-1-binding sequence; Electrophoretic mobility shift assay; GROα; Growth-regulated oncogene α; IL; Interleukin; MAPK; Mitogen-activated protein kinase; RT-PCR; Reverse transcription-polymerase chain reaction; TNFα; Transcriptional regulation; Tumor microenvironment; Tumor necrosis factor α; siRNA; small-interfering RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Blotting, Northern
  • Blotting, Western
  • Cell Movement
  • Chemokine CXCL1 / genetics*
  • Chemokine CXCL1 / metabolism
  • Early Growth Response Protein 1 / antagonists & inhibitors
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System / genetics
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation / genetics
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Chemokine CXCL1
  • Early Growth Response Protein 1
  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha