ArticleProceedings of the National Academy of Sciences of the United States of America2000
Activation of the human estrogen receptor by the antiestrogens ICI 182,780 and tamoxifen in yeast genetic systems: implications for their mechanism of action.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 55 citations in OpenAlex.
- Alternative promoters and splicing create multiple functionally distinct isoforms of oestrogen receptor alpha in breast cancer and healthy tissues.Cancer medicine · 2023Article
- 2',3',4'-Trihydroxychalcone changes estrogen receptor α regulation of genes and breast cancer cell proliferation by a reprogramming mechanism.Molecular medicine (Cambridge, Mass.) · 2022Article
- 27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- A transcriptomics model of estrogen action in the ovine fetal hypothalamus: evidence for estrogenic effects of ICI 182,780.Physiological reports · 2018Article
- (Anti-)estrogenic and (anti-)androgenic effects in wastewater during advanced treatment: comparison of three in vitro bioassays.Environmental science and pollution research international · 2018Article
- Temporal and concentration-dependent effects of oestradiol on neural pathways mediating sexual receptivity.Journal of neuroendocrinology · 2013Review
- Article
- Fluorescently-Labeled Estradiol Internalization and Membrane Trafficking in Live N-38 Neuronal Cells Visualized with Total Internal Reflection Fluorescence Microscopy.Journal of steroids & hormonal science · 2013Article
- 17β-Estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site.Endocrinology · 2012Article
- Anatomically-specific actions of oestrogen receptor in the developing female rat brain: effects of oestradiol and selective oestrogen receptor modulators on progestin receptor expression.Journal of neuroendocrinology · 2012Article
- Estrogen receptor-alpha 36 mediates mitogenic antiestrogen signaling in ER-negative breast cancer cells.PloS one · 2012Article
- Okadaic acid induces tau phosphorylation in SH-SY5Y cells in an estrogen-preventable manner.Brain research · 2010Article
- Interdependence of platelet-derived growth factor and estrogen-signaling pathways in inducing neonatal rat testicular gonocytes proliferation.Biology of reproduction · 2010Article
- Membrane estrogen receptor-alpha levels predict estrogen-induced ERK1/2 activation in MCF-7 cells.Breast cancer research : BCR · 2005Article
- Reduction of post injury neointima formation due to 17beta-estradiol and phytoestrogen treatment is not influenced by the pure synthetic estrogen receptor antagonist ICI 182,780 in vitro.BMC cardiovascular disorders · 2002Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The antiestrogens tamoxifen and ICI 182,780 have been portrayed as competitive antagonists of the estrogen binding site of the alpha-form of the human estrogen receptor (ER). However, in functional studies, neither compound has consistently been able to block estradiol-induced transcription. In this report, three yeast genetic systems were used to investigate the effects of tamoxifen and ICI 182,780 on ER dimerization, transcriptional activation, and the interaction of the receptor with a coactivator, RIP140. Tamoxifen and ICI 182,780 were able to induce ER dimerization and ER-dependent transcription, albeit at up to 15,000-fold higher concentrations than that of estradiol. In the presence of RIP140, the transcription response maximum was increased up to 30-fold for estradiol and both antiestrogens. Whole yeast cell [(3)H]estradiol binding studies demonstrated that tamoxifen could displace the estradiol from the ER, whereas ICI 182,780 treatment resulted in a 4-fold increase in [(3)H]estradiol binding to the receptor. No antagonism of estradiol was observed with tamoxifen or ICI 182,780 in any of the yeast models employed. We have concluded that the antiestrogen activity of compounds like tamoxifen and ICI 182,780 is not caused by their ability to competitively antagonize estradiol binding to the hormone binding site, but possibly by their ability to induce ER-dependent transcription, which in mammalian systems would result in receptor down-regulation. Compounds such as tamoxifen act through the hormone binding site, whereas ICI 182,780 may cause receptor activation through an allosteric binding site.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.