Estrogen-induced c-fos protooncogene expression in MCF-7 human breast cancer cells: role of estrogen receptor Sp1 complex formation

Endocrinology. 1998 Apr;139(4):1981-90. doi: 10.1210/endo.139.4.5870.


17Beta-estradiol (E2) induces c-fos protooncogene expression in MCF-7 human breast cancer cells, and previous studies in HeLa cells identified an imperfect palindromic estrogen-responsive element (-1212 to -1200) that was required for trans-activation. In contrast, the estrogen-responsive element was not required for E2 responsiveness in MCF-7 cells, and using a series of constructs containing wild-type (pF1) and mutant 5'-flanking sequences (-1220 to -1155) from the c-fos protooncogene promoter in transient transfection assays, it was shown that a GC-rich motif (5'-GGGGCGTGG) containing an imperfect Sp1-binding site was required for hormone-induced activity. This sequence also bound Sp1 protein in gel mobility shift assays, and coincubation with the estrogen receptor (ER) enhanced Sp1-DNA binding. E2 and 4'-hydroxytamoxifen, but not ICI 164,384, induced reporter gene activity in cells transiently transfected with pF1. E2 induced reporter gene activity in MDA-MB-231 breast cancer cells transiently cotransfected with pF1 and wild-type ER or variant ER in which the DNA-binding domain was deleted (HE11); plasmids expressing N-terminal or C-terminal domains of the ER containing activator function-1 or -2, respectively, were inactive in these assays. In contrast, only wild-type ER mediated 4'-hydroxytamoxifen-induced activity. Induction of c-fos protooncogene expression by E2 in MCF-7 cells is dependent on the formation of a transcriptionally active ER/Sp1 complex that binds to a GC-rich enhancer element.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Breast Neoplasms / metabolism*
  • Chloramphenicol O-Acetyltransferase / genetics
  • Estradiol / pharmacology*
  • Estrogen Antagonists / pharmacology
  • Gene Deletion
  • Gene Expression / drug effects*
  • Genes, fos / genetics*
  • Humans
  • Mutagenesis
  • Promoter Regions, Genetic
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recombinant Fusion Proteins
  • Sp1 Transcription Factor / metabolism*
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Transfection
  • Tumor Cells, Cultured


  • Estrogen Antagonists
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Sp1 Transcription Factor
  • Tamoxifen
  • afimoxifene
  • Estradiol
  • Chloramphenicol O-Acetyltransferase