ArticleScience advances2016
Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.
- Association of progesterone receptor status with breast cancer prognosis: a meta-analysis.World journal of surgical oncology · 2025Pooled it
- Meta-analysis of integrated ChIP-seq and transcriptome data revealed genomic regions affected by estrogen receptor alpha in breast cancer.BMC medical genomics · 2023Pooled it
- Asymmetric cross-reactivity of nuclear receptors reveals an evolutionary buffer between estrogen and androgen signaling.iScience · 2026Article
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Integrating chemical structure and high-throughput transcriptomics for mechanistically interpretable Tox21 bioactivity prediction.Journal of cheminformatics · 2026Article
- Estrogen receptor alpha and beta chromatin interactions govern ovarian folliculogenesis but dissipate during ovulation.Endocrinology · 2026Article
- Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context of ESR1 mutation.NPJ breast cancer · 2026Article
- Synthetic estrogen and progestin effects on the myogenic program following damage in C2C12 murine myoblasts.Physiological reports · 2026Article
- Ligand-Dependent and -Independent Functions of Activation Function 1 of Progesterone Receptor in Genome-Wide Gene Regulation and in Cell Proliferation and Apoptosis of Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Androgen Signaling Represses Homeobox C9, an Inhibitor of Androgen Receptor, in Prostate Cancer Cells.International journal of molecular sciences · 2026Article
- ERFrontiers in oncology · 2026Review
- Proteomics analysis reveals progesterone receptor induced mitochondria-mediated apoptosis in breast cancer cells.Scientific reports · 2025Article
- Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context ofbioRxiv : the preprint server for biology · 2025Article
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- Evaluation of progesterone receptors with different cutoff values according to menopausal status in hormone-positive early breast cancer.Scientific reports · 2025Article
- Maf1 cooperates with progesterone receptor to repress RNA polymerase III transcription of select tRNAs.Nucleic acids research · 2025Article
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
- Isoform-Specific Gene Regulation by Progesterone Receptors Drives Divergent Phenotypes in Breast Cancer Cells.bioRxiv : the preprint server for biology · 2025Article
- dFLASH; dual FLuorescent transcription factor activity sensor for histone integrated live-cell reporting and high-content screening.Nature communications · 2025Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER(+) (estrogen receptor-positive)/PR(+) human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER(+)/PR(+) breast cancers should be explored.
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What OpenQuestion holds
Registered trials
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.