ArticleOncotarget2018
Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis 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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- 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
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Dual Role of Tamoxifen in Enhancing STING and CEACAM1 Expression to Prime a Favorable Tumor Microenvironment for Anti-TIM3 Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nutrition Across the Life Course and Risk of Young-Onset Breast Cancer: Mechanisms, Evidence, and Prevention Opportunities.Nutrients · 2026Review
- Characterization of Isoorientin and Paeoniflorin as Botanical Glucocorticoid Receptor Modulators from White Peony and Chasteberry.Nutrients · 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
- 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
- Isoform-Specific Gene Regulation by Progesterone Receptors Drives Divergent Phenotypes in Breast Cancer Cells.bioRxiv : the preprint server for biology · 2025Article
- Structural proteomics defines a sequential priming mechanism for the progesterone receptor.Nature communications · 2025Article
- Article
- Introducing a New Hypothesis in the Genesis of Breast Cancer: An Integrative Review.Breast cancer (Dove Medical Press) · 2025Review
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- Adjuvant chemotherapy and survival in males aged 70 years or older with breast cancer: a population-based retrospective study.BMC geriatrics · 2024Article
- ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.NPJ breast cancer · 2023Article
- Reevaluating the Role of Progesterone in Ovarian Cancer: Is Progesterone Always Protective?Endocrine reviews · 2023Article
- Expression of Progesterone Receptor A as an Independent Negative Prognosticator for Cervical Cancer.International journal of molecular sciences · 2023Article
- Article
- Computational approaches to identify a novel binding site of BHPI on estrogen receptor alpha.Steroids · 2022Article
- StackPR is a new computational approach for large-scale identification of progesterone receptor antagonists using the stacking strategy.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR-targeted therapies to the clinic.
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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.