The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling
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.
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ICI 182,780 is a pure anti-estrogen.
“we treated mice with either the anti-estrogen ICI 182,780 (ICI), a “pure” anti-estrogen [17], 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), a potent ERα agonist [18], or ditolylguanidine (DTG), a sigma-1 and −2 receptor agonist.”
From Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis (2015) · cites this paper as [17]
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- Authors
- Dauvois, S., White, R., & Parker, M. G.
- Affiliations
- Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 1993-12-01
- Volume
- 106
- Issue
- 4
- Pages
- 1377-1388
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2147673480
- Cited by
- 522
- References
- 45
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 14 · 2015: 15 · 2014: 17 · 2013: 19 · 2012: 15
- FWCI
- 7.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- estrogen receptor, fulvestrant, tamoxifen, antiestrogens, nucleocytoplasmic shuttling, nuclear uptake, subcellular localization, heterokaryons, estradiol, ligand binding, nuclear export
- MeSH terms
- Fulvestrant, Amino Acid Sequence, Animals, Biological Transport, Cell Compartmentation, Cell Nucleus, Cells, Cultured, Chlorocebus aethiops, Cytoplasm, Estradiol, Estrogen Antagonists, Hybrid Cells, Molecular Sequence Data, Oligomycins, Receptors, Estrogen, Recombinant Proteins, Tamoxifen, Transfection, Sequence Homology, Amino Acid, Mice, Polyunsaturated Alkamides
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