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PMID: 2118104 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

The EMBO journal ·Vol. 9 ·No. 9 ·1990-09-00 ·Pages 2811-8

Berry M, Metzger D, Chambon P

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.

MeSH Terms
Animals Chick Embryo Chloramphenicol O-Acetyltransferase/genetics,metabolism Estradiol/analogs & derivatives,pharmacology Estrogen Antagonists/pharmacology Fibroblasts/drug effects,metabolism HeLa Cells/drug effects,metabolism Humans Polyunsaturated Alkamides Promoter Regions, Genetic/drug effects Receptors, Estrogen/genetics,metabolism Saccharomyces cerevisiae/enzymology,genetics Tamoxifen/analogs & derivatives,pharmacology Transcription, Genetic/drug effects Transfection beta-Galactosidase/genetics,metabolism
Chemicals
Estrogen Antagonists Polyunsaturated Alkamides Receptors, Estrogen Tamoxifen afimoxifene Estradiol ICI 164384 Chloramphenicol O-Acetyltransferase beta-Galactosidase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Berry M
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
Metzger D
Chambon P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-09-00
Pages
2811-8
Language
English
Region
England
NLM ID
8208664
PMCID
PMC551992
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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