Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen

EMBO J. 1990 Sep;9(9):2811-8.

Abstract

Various oestrogen responsive reporter genes and vectors expressing truncated or chimeric human oestrogen receptors (hER) containing either of the two independent hER transcriptional activation functions (TAF-1 and TAF-2) have been transfected into HeLa cells, chicken embryo fibroblast (CEF) or yeast cells to investigate the agonistic activity of the anti-oestrogen 4-hydroxytamoxifen (OHT). We demonstrate that the agonistic effect of OHT on the whole hER is due to the cell-type and promoter-context dependent activity of TAF-1. In similar experiments, we show that the anti-oestrogen, ICI 164,384, does not exhibit any oestrogenic activity and, therefore, acts always as a pure antagonist, even though it does not inhibit the activity of the isolated TAF-1. We also confirm that the wild type human oestrogen receptor has no ligand independent transcriptional activity. The implications of our results for the variable antagonist/agonist activity of anti-oestrogens in vivo are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism
  • Humans
  • Polyunsaturated Alkamides
  • Promoter Regions, Genetic / drug effects*
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology
  • Transcription, Genetic / drug effects
  • Transfection
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Estrogen Antagonists
  • Polyunsaturated Alkamides
  • Receptors, Estrogen
  • Tamoxifen
  • afimoxifene
  • Estradiol
  • ICI 164384
  • Chloramphenicol O-Acetyltransferase
  • beta-Galactosidase