The zinc finger transcription factor EGR-1 impedes interleukin-1-inducible tumor growth arrest

Stephen F. Sells, Sumathi Muthukumar, Vikas P. Sukhatme, Scott A. Crist, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Interleukin-1 (IL-1) is a growth arrest signal for diverse human tumor cell lines. We report here that the action of this cytokine in melanoma cells is associated with induction of EGR-1, a zinc finger protein that activates gene transcription. Both growth arrest and EGR-1 are induced via the type I receptor of IL-1. To determine the role of EGR-1 in IL-1 action in melanoma cells, we used a chimera expressing the transrepression domain of the Wilms' tumor gene, WT1, and the DNA binding domain of Egr-1. This chimera competitively inhibited EGR-1-dependent transactivation via the GC-rich DNA binding sequence, indicating that it acted as a functional dominant negative mutant of Egr-1. Melanoma cell lines stably transfected with the dominant negative mutant construct were supersensitive to IL-1 and showed accelerated G0/G1 growth arrest compared with the parental cell line. The effect of the dominant negative mutant construct was mimicked by addition of an antisense Egr-1 oligomer to the culture medium of the parental cells: the oligomer inhibited EGR-1 expression and accelerated the growth-inhibitory response to IL-1. These data imply that EGR-1 acts to delay IL-1-mediated tumor growth arrest.

Original languageEnglish
Pages (from-to)682-692
Number of pages11
JournalMolecular and Cellular Biology
Issue number2
StatePublished - Feb 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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