Egr-1 is activated by 17β-estradiol in MCF-7 cells by mitogen-activated protein kinase-dependent phosphorylation of ELK-1

Chien Cheng Chen, Wan Ru Lee, Stephen Safe

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Early growth response-1 (Egr-1) is an immediate-early gene induced by E2 in the rodent uterus and breast cancer cells. E2 induces Egr-1 mRNA and protein levels in MCF-7 human breast cancer cells and reporter gene activity in cells transfected with pEgr-1A, a construct containing the -600 to +12 region of the Egr-1 promoter linked to the firefly luciferase gene. Deletion analysis of the Egr-1 promoter identified a minimal E2-responsive region of the promoter that contained serum response element (SRE)3 (-376 to -350) which bound Elk-1 and serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a mitogen-activated protein kinase kinase inhibitor, but not by LY294002, an inhibitor of phosphatidylinositol-3-kinase (PI3-K). These results contrasted with hormone-dependent activation of the SRE in the c-fos promoter, which was inhibited by both PD98059 and LY294002. Differences in activation of the SREs in Egr-1 and c-fos were related to promoter sequence, which defines the affinities of Elk-1 and SRF to their respective binding sites. Thus, Egr-1, like c-fos, is activated through non-genomic (extranuclear) pathways of estrogen action in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)1063-1074
Number of pages12
JournalJournal of Cellular Biochemistry
Volume93
Issue number5
DOIs
StatePublished - 2004

Keywords

  • Egr-1
  • Elk-1
  • Estrogens
  • Extranuclear
  • MAPK

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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