ArticleJournal of experimental & clinical cancer research : CR2015
ERRγ target genes are poor prognostic factors in Tamoxifen-treated breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
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- Ubiquitin-independent pathway regulates the RIT1-MAPK pathway in chordoma progression.Cell death & disease · 2025Article
- Integrated Nanopore and short-read RNA sequencing identifies dysregulation of METTL3- m6A modifications in endocrine therapy- sensitive and resistant breast cancer cells.Functional & integrative genomics · 2025Article
- Insight into the Binding Interaction between PEDCs and hERRγ Utilizing Molecular Docking and Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2024Article
- Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression.International journal of molecular sciences · 2022Review
- Molecular dynamics of estrogen-related receptors and their regulatory proteins: roles in transcriptional control for endocrine and metabolic signaling.Anatomical science international · 2022Review
- ERRJournal of oncology · 2022Article
- Estrogen-Related Receptors Gene Expression and Copy Number Alteration Association With the Clinicopathologic Characteristics of Breast Cancer.Breast cancer : basic and clinical research · 2022Article
- Emerging Roles of COX7RP and Mitochondrial Oxidative Phosphorylation in Breast Cancer.Frontiers in cell and developmental biology · 2022Review
- Excavating the pathogenic gene of breast cancer based on high throughput data of tumor and somatic reprogramming.Cell cycle (Georgetown, Tex.) · 2021Article
- Nuclear receptors in the kidney during health and disease.Molecular aspects of medicine · 2021Review
- Epigenetic Study of Esophageal Carcinoma Based on Methylation, Gene Integration and Weighted Correlation Network Analysis.OncoTargets and therapy · 2021Article
- Estrogen-Related Receptor γ Agonist DY131 Ameliorates Lipopolysaccharide-Induced Acute Liver Injury.Frontiers in pharmacology · 2021Article
- Sophoridine exerts tumor-suppressive activities via promoting ESRRG-mediated β-catenin degradation in gastric cancer.BMC cancer · 2020Article
- Article
- Alcohol and DNA Methylation: An Epigenome-Wide Association Study in Blood and Normal Breast Tissue.American journal of epidemiology · 2019Article
- Integrative Deep Learning for Identifying Differentially Expressed (DE) Biomarkers.Computational and mathematical methods in medicine · 2019Article
- The PGC-1/ERR network and its role in precision oncology.NPJ precision oncology · 2019Review
- The modulatory role of low concentrations of bisphenol A on tamoxifen-induced proliferation and apoptosis in breast cancer cells.Environmental science and pollution research international · 2019Article
- Elevated expression of PTCD3 correlates with tumor progression and predicts poor prognosis in patients with prostate cancer.Molecular medicine reports · 2018Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOne-third of estrogen (ER+) and/or progesterone receptor-positive (PGR+) breast tumors treated with Tamoxifen (TAM) do not respond to initial treatment, and the remaining 70% are at risk to relapse in the future. Estrogen-related receptor gamma (ESRRG, ERRγ) is an orphan nuclear receptor with broad, structural similarities to classical ER that is widely implicated in the transcriptional regulation of energy homeostasis. We have previously demonstrated that ERRγ induces resistance to TAM in ER+ breast cancer models, and that the receptor's transcriptional activity is modified by activation of the ERK/MAPK pathway. We hypothesize that hyper-activation or over-expression of ERRγ induces a pro-survival transcriptional program that impairs the ability of TAM to inhibit the growth of ER+ breast cancer. The goal of the present study is to determine whether ERRγ target genes are associated with reduced distant metastasis-free survival (DMFS) in ER+ breast cancer treated with TAM.
methodsRaw gene expression data was obtained from 3 publicly available breast cancer clinical studies of women with ER+ breast cancer who received TAM as their sole endocrine therapy. ERRγ target genes were selected from 2 studies that published validated chromatin immunoprecipitation (ChIP) analyses of ERRγ promoter occupancy. Kaplan-Meier estimation was used to determine the association of ERRγ target genes with DMFS, and selected genes were validated in ER+, MCF7 breast cancer cells that express exogenous ERRγ.
resultsThirty-seven validated receptor target genes were statistically significantly altered in women who experienced a DM within 5 years, and could classify several independent studies into poor vs. good DMFS. Two genes (EEF1A2 and PPIF) could similarly separate ER+, TAM-treated breast tumors by DMFS, and their protein levels were measured in an ER+ breast cancer cell line model with exogenous ERRγ. Finally, expression of ERRγ and these two target genes are elevated in models of ER+ breast cancer with hyperactivation of ERK/MAPK.
conclusionsERRγ signaling is associated with poor DMFS in ER+, TAM-treated breast cancer, and ESRRG, EEF1A2, and PPIF comprise a 3-gene signaling node that may contribute to TAM resistance in the context of an active ERK/MAPK pathway.
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