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.
Fiche publication
Date publication
septembre 1990
Journal
The EMBO journal
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel
Tous les auteurs :
Berry M, Metzger D, Chambon P
Lien Pubmed
Résumé
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.
Mots clés
Animals, Chick Embryo, Chloramphenicol O-Acetyltransferase, genetics, Estradiol, analogs & derivatives, Estrogen Antagonists, pharmacology, Fibroblasts, drug effects, HeLa Cells, drug effects, Humans, Polyunsaturated Alkamides, Promoter Regions, Genetic, drug effects, Receptors, Estrogen, genetics, Saccharomyces cerevisiae, enzymology, Tamoxifen, analogs & derivatives, Transcription, Genetic, drug effects, Transfection, beta-Galactosidase, genetics
Référence
EMBO J.. 1990 Sep;9(9):2811-8