ArticleEndocrinology2019
Phosphorylated Progesterone Receptor Isoforms Mediate Opposing Stem Cell and Proliferative Breast Cancer Cell Fates.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
39 citing papers in PubMed, 57 citations in OpenAlex.
- Altered Progesterone Receptor Isoform Expression in Endometrial Cells: A Preliminary Immunohistochemical Study in Endometriosis.Journal of clinical medicine · 2026Article
- A proteogenomic RNA processing mechanism drives sex differences in meningioma.Research square · 2026Article
- Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results.NPJ breast cancer · 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
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- 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
- Structural proteomics defines a sequential priming mechanism for the progesterone receptor.Nature communications · 2025Article
- Site-specific O-GlcNAcylation of progesterone receptor (PR) supports PR attenuation of interferon stimulated genes (ISGs) and tumor growth in breast cancer.The Journal of biological chemistry · 2024Article
- Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer.Endocrinology · 2024Article
- Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk.Cell stem cell · 2024Article
- The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol.Oncology letters · 2024Article
- Insulin-like growth factor binding protein-6 modulates proliferative antagonism in response to progesterone in breast cancer.Frontiers in endocrinology · 2024Article
- Reevaluating the Role of Progesterone in Ovarian Cancer: Is Progesterone Always Protective?Endocrine reviews · 2023Article
- A New Diterpenoid of IndonesianMolecules (Basel, Switzerland) · 2023Article
- Variable Intrinsic Expression of Immunoregulatory Biomarkers in Breast Cancer Cell Lines, Mammospheres, and Co-Cultures.International journal of molecular sciences · 2023Article
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Unexplored Functions of Sex Hormones in Glioblastoma Cancer Stem Cells.Endocrinology · 2022Review
- Ablation of Akt2 and AMPKActa pharmaceutica Sinica. B · 2021Article
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Progesterone receptors (PRs) are key modifiers of estrogen receptor (ER) target genes and drivers of luminal breast cancer progression. Total PR expression, rather than isoform-specific PR expression, is measured in breast tumors as an indicator of functional ER. We identified phenotypic differences between PR-A and PR-B in luminal breast cancer models with a focus on tumorsphere biology. Our findings indicated that PR-A is a dominant driver of cancer stem cell (CSC) expansion in T47D models, and PR-B is a potent driver of anchorage-independent proliferation. PR-A+ tumorspheres were enriched for aldehyde dehydrogenase (ALDH) activity, CD44+/CD24-, and CD49f+/CD24- cell populations relative to PR-B+ tumorspheres. Progestin promoted heightened expression of known CSC-associated target genes in PR-A+ but not PR-B+ cells cultured as tumorspheres. We report robust phosphorylation of PR-A relative to PR-B Ser294 and found that this residue is required for PR-A-induced expression of CSC-associated genes and CSC behavior. Cells expressing PR-A S294A exhibited impaired CSC phenotypes but heightened anchorage-independent cell proliferation. The PR target gene and coactivator, FOXO1, promoted PR phosphorylation and tumorsphere formation. The FOXO1 inhibitor (AS1842856) alone or combined with onapristone (PR antagonist), blunted phosphorylated PR, and tumorsphere formation in PR-A+ and PR-B+ T47D, MCF7, and BT474 models. Our data revealed unique isoform-specific functions of phosphorylated PRs as modulators of distinct and opposing pathways relevant to mechanisms of late recurrence. A clear understanding of PR isoforms, phosphorylation events, and the role of cofactors could lead to novel biomarkers of advanced tumor behavior and reveal new approaches to pharmacologically target CSCs in luminal breast cancer.
Indexed as
Identifiers
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.