The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling

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  • Sophie Dauvois
    Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK
  • Roger White
    Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK
  • Malcolm G. Parker
    Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK

説明

<jats:title>ABSTRACT</jats:title> <jats:p>The mouse estrogen receptor was shown to be constantly shuttling between the nucleus and cytoplasm although under steady-state conditions it is detected predomi-nantly in the cell nucleus in both the absence and pres-ence of estradiol. Shuttling was demonstrated by moni-toring the transfer of protein between nuclei in heterokaryons and by examining the subcellular distri-bution of mutant receptors. In the presence of the par-tial antiestrogen 4-hydroxytamoxifen the receptor was retained in the nucleus whereas it accumulated in the cytoplasm when cells were treated with the pure antie-strogen ICI 182780. The effect of the pure antiestrogen was to inhibit nucleocytoplasmic shuttling of the recep-tor by blocking its nuclear uptake. Thus although ligand binding is not required by the estrogen receptor to undergo nucleocytoplasmic shuttling, this process can be disrupted by the binding of a pure antiestrogen.</jats:p>

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