The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling

TLDR

The mouse estrogen receptor constantly shuttles between nucleus and cytoplasm, yet remains predominantly nuclear under steady‑state conditions with or without estradiol. Shuttling was demonstrated by tracking protein transfer between nuclei in heterokaryons and by examining the subcellular distribution of mutant receptors. The pure antiestrogen ICI 182780 blocks nuclear uptake of the estrogen receptor, causing cytoplasmic accumulation and inhibiting its nucleocytoplasmic shuttling, whereas 4‑hydroxytamoxifen retains the receptor in the nucleus.

Abstract

ABSTRACT 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.