ArticleThe Journal of biological chemistry2013
Interaction of glucocorticoid receptor (GR) with estrogen receptor (ER) α and activator protein 1 (AP1) in dexamethasone-mediated interference of ERα activity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Chronic psychosocial stress: a role in breast cancer etiology?Frontiers in oncology · 2026Pooled it
- Hormonal mechanisms of women's risk in the face of traumatic stress.Proceedings of the National Academy of Sciences of the United States of America · 2025Trial
- Gender Bias in Human Systemic Lupus Erythematosus: A Problem of Steroid Receptor Action?Frontiers in immunology · 2018Trial
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Signaling Under Stress: Targeting the Glucocorticoid Receptor in Cancer.Cancer research · 2026Review
- Premedication with steroids in breast cancer - supportive treatment or tumour growth promotion?Magyar onkologia · 2026Review
- Estrogen receptor alpha and beta chromatin interactions govern ovarian folliculogenesis but dissipate during ovulation.Endocrinology · 2026Article
- Dexamethasone Suppresses Already Low Estrogen Receptor Levels in Meningiomas.International journal of molecular sciences · 2026Review
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Marine-Derived Steroids for Cancer Treatment: Search for Potential Selective Glucocorticoid Receptor Agonists/Modulators (SEGRAMs).Marine drugs · 2025Review
- NF1-depleted ERScience translational medicine · 2025Article
- Stress and parental behaviors.Neuroscience research · 2025Review
- Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.Acta pharmaceutica Sinica. B · 2025Article
- Transcriptional induction by ecdysone in Drosophila salivary glands involves an increase in chromatin accessibility and acetylation.Nucleic acids research · 2025Article
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Signature analysis of high-throughput transcriptomics screening data for mechanistic inference and chemical grouping.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.Bioscience reports · 2024Article
- Upregulation of coagulation factor V by glucocorticoid in the preovulatory follicles of zebrafish.The Journal of steroid biochemistry and molecular biology · 2024Article
- Liver-specific glucocorticoid action in alcoholic liver disease: Study of glucocorticoid receptor knockout and knockin mice.Liver research (Beijing, China) · 2024Article
- Dihydrotestosterone induces arterial stiffening in female mice.Biology of sex differences · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of glucocorticoids in the inhibition of estrogen (17-β-estradiol (E2))-regulated estrogen receptor (ER)-positive breast cancer cell proliferation is well established. We and others have seen that synthetic glucocorticoid dexamethasone (Dex) antagonizes E2-stimulated endogenous ERα target gene expression. However, how glucocorticoids negatively regulate the ERα signaling pathway is still poorly understood. ChIP studies using ERα- and glucocorticoid receptor (GR)-positive MCF-7 cells revealed that GR occupies several ERα-binding regions (EBRs) in cells treated with E2 and Dex simultaneously. Interestingly, there was little or no GR loading to these regions when cells were treated with E2 or Dex alone. The E2+Dex-dependent GR recruitment is associated with the displacement of ERα and steroid receptor coactivator-3 from the target EBRs leading to the repression of ERα-mediated transcriptional activation. The recruitment of GR to EBRs requires assistance from ERα and FOXA1 and is facilitated by AP1 binding within the EBRs. The GR binding to EBRs is mediated via direct protein-protein interaction between the GR DNA-binding domain and ERα. Limited mutational analyses indicate that arginine 488 located within the C-terminal zinc finger domain of the GR DNA-binding domain plays a critical role in stabilizing this interaction. Together, the results of this study unravel a novel mechanism involved in glucocorticoid inhibition of ERα transcriptional activity and E2-mediated cell proliferation and thus establish a foundation for future exploitation of the GR signaling pathway in the treatment of ER-positive breast cancer.
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