ArticleMolecular cancer research : MCR2016
GR and ER Coactivation Alters the Expression of Differentiation Genes and Associates with Improved ER+ Breast Cancer Outcome.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis.BMC cancer · 2020Pooled it
- 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
- Perioperative psycho-behavioral stress promotes cancer metastasis beyond the impact of surgery: Neuroendocrine and tumor molecular mediating mechanisms.Brain, behavior, & immunity - health · 2026Article
- Premedication with steroids in breast cancer - supportive treatment or tumour growth promotion?Magyar onkologia · 2026Review
- Activated glucocorticoid receptor is an estrogen receptor silencer in ER+ metastatic breast cancer.EMBO molecular medicine · 2026Article
- Review
- Marine-Derived Steroids for Cancer Treatment: Search for Potential Selective Glucocorticoid Receptor Agonists/Modulators (SEGRAMs).Marine drugs · 2025Review
- Levonorgestrel-induced modulation of triple negative breast cancer proliferation via glucocorticoid receptor.3 Biotech · 2025Article
- Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors.Biomedicines · 2025Article
- The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics.Scientific reports · 2025Article
- High tumor glucocorticoid receptor expression in early-stage, triple-negative breast cancer is associated with increased T-regulatory cell infiltration.Breast cancer research and treatment · 2025Article
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies.International journal of molecular sciences · 2024Article
- Glucocorticoid receptors orchestrate a convergence of host and cellular stress signals in triple negative breast cancer.The Journal of steroid biochemistry and molecular biology · 2024Review
- Upregulation of coagulation factor V by glucocorticoid in the preovulatory follicles of zebrafish.The Journal of steroid biochemistry and molecular biology · 2024Article
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- Glucocorticoid receptor: a harmonizer of cellular plasticity in breast cancer-directs the road towards therapy resistance, metastatic progression and recurrence.Cancer metastasis reviews · 2024Review
- The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer.Genome biology · 2024Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledIn estrogen receptor (ER)-negative breast cancer, high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER(+) relapse-free survival (RFS; independently of progesterone receptor expression). To understand the mechanism by which GR expression is associated with a better ER(+) breast cancer outcome, the global effect of GR-mediated transcriptional activation in ER(+) breast cancer cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing in ER(+)/GR(+) MCF-7 cells revealed that upon coactivation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased GR chromatin association was observed at ER, FOXO, and AP1 response elements. In addition, ER associated with GR response elements, suggesting that ER and GR interact in a complex. Coactivation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g., KDM4B, VDR) and inhibiting the Wnt signaling pathway (IGFBP4). Finally, expression of these individual prodifferentiation genes was associated with significantly improved RFS in ER(+) breast cancer patients. Together, these data suggest that the coexpression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage breast cancer by coordinating the altered expression of genes favoring differentiation. IMPLICATIONS: The interaction between ER and GR activity highlights the importance of context-dependent nuclear receptor function in cancer. Mol Cancer Res; 14(8); 707-19. ©2016 AACR.
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