ArticleJournal of the National Cancer Institute2019
TP53 Status as a Determinant of Pro- vs Anti-Tumorigenic Effects of Estrogen Receptor-Beta in Breast Cancer.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Mutant p53 binds and controls estrogen receptor activity to drive endocrine resistance in ovarian cancer.Genes & development · 2026Article
- Role of ERβ in Triple-Negative Breast Cancer Associated with p53 and Androgen Receptor.International journal of molecular sciences · 2025Article
- Interaction between Estrogen Receptors and p53: A Broader Role for Tamoxifen?Endocrinology · 2025Review
- Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review).Oncology letters · 2025Review
- Significance of dysregulated M2 macrophage andTranslational cancer research · 2024Article
- Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple-Negative Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Review
- Therapeutic Role of Tamoxifen for Triple-Negative Breast Cancer: Leveraging the Interaction Between ERβ and Mutant p53.The oncologist · 2023Article
- Estrogen Receptor β4 Regulates Chemotherapy Resistance and Induces Cancer Stem Cells in Triple Negative Breast Cancer.International journal of molecular sciences · 2023Article
- Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research.Frontiers in cell and developmental biology · 2023Review
- Review
- Differences in somatic TP53 mutation type in breast tumors by race and receptor status.Breast cancer research and treatment · 2022Article
- Article
- The Significance of Tumor Microenvironment Score for Breast Cancer Patients.BioMed research international · 2022Article
- Loss of peptidase D binding restores the tumor suppressor functions of oncogenic p53 mutants.Communications biology · 2021Article
- Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition.Cancer cell international · 2021Article
- The Chk2-PKM2 axis promotes metabolic control of vasculogenic mimicry formation in p53-mutated triple-negative breast cancer.Oncogene · 2021Article
- Estrogen Receptor-Alpha and p53 Status as Regulators of AMPK and mTOR in Luminal Breast Cancer.Cancers · 2021Article
- Application value of conventional ultrasound combined with shear wave elastography in diagnosing triple negative breast cancer.Gland surgery · 2021Article
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
backgroundAnti-tumorigenic vs pro-tumorigenic roles of estrogen receptor-beta (ESR2) in breast cancer remain unsettled. We investigated the potential of TP53 status to be a determinant of the bi-faceted role of ESR2 and associated therapeutic implications for triple negative breast cancer (TNBC).
methodsESR2-TP53 interaction was analyzed with multiple assays including the in situ proximity ligation assay. Transcriptional effects on TP53-target genes and cell proliferation in response to knocking down or overexpressing ESR2 were determined. Patient survival according to ESR2 expression levels and TP53 mutation status was analyzed in the basal-like TNBC subgroup in the Molecular Taxonomy of Breast Cancer International Consortium (n = 308) and Roswell Park Comprehensive Cancer Center (n = 46) patient cohorts by univariate Cox regression and log-rank test. All statistical tests are two-sided.
resultsESR2 interaction with wild-type and mutant TP53 caused pro-proliferative and anti-proliferative effects, respectively. Depleting ESR2 in cells expressing wild-type TP53 resulted in increased expression of TP53-target genes CDKN1A (control group mean [SD] = 1 [0.13] vs ESR2 depletion group mean [SD] = 2.08 [0.24], P = .003) and BBC3 (control group mean [SD] = 1 [0.06] vs ESR2 depleted group mean [SD] = 1.92 [0.25], P = .003); however, expression of CDKN1A (control group mean [SD] = 1 [0.21] vs ESR2 depleted group mean [SD] = 0.56 [0.12], P = .02) and BBC3 (control group mean [SD] = 1 [0.03] vs ESR2 depleted group mean [SD] = 0.55 [0.09], P = .008) was decreased in cells expressing mutant TP53. Overexpressing ESR2 had opposite effects. Tamoxifen increased ESR2-mutant TP53 interaction, leading to reactivation of TP73 and apoptosis. High levels of ESR2 expression in mutant TP53-expressing basal-like tumors is associated with better prognosis (Molecular Taxonomy of Breast Cancer International Consortium cohort: log-rank P = .001; hazard ratio = 0.26, 95% confidence interval = 0.08 to 0.84, univariate Cox P = .02).
conclusionsTP53 status is a determinant of the functional duality of ESR2. Our study suggests that ESR2-mutant TP53 combination prognosticates survival in TNBC revealing a novel strategy to stratify TNBC for therapeutic intervention potentially by repurposing tamoxifen.
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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.