ArticleThe Journal of clinical endocrinology and metabolism2021
Progesterone Receptors Promote Quiescence and Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models.
Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Pathogenesis of peritoneal high-grade serous carcinoma after risk-reducing surgery: a systematic review.The journal of pathology. Clinical research · 2025Pooled it
- Integrative Multi-Omics and Experimental Validation Define RELB as an Immune-Related Prognostic Driver in Ovarian Cancer.Chemical biology & drug design · 2026Article
- Defining the Role of Progesterone Signaling in High-Grade Serous Ovarian Cancer Using Fallopian Tube Models.Research square · 2026Article
- Individualised progesterone receptor modulator prevention strategies for triple-negative breast cancer in BRCA1 pathogenic variant carriers.NPJ breast cancer · 2026Review
- 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
- Signaling Pathway Dissection After Progesterone Receptor Enhancement in an Immortalized Pre-Cancer Fallopian Tube Epithelial Cell Line.International journal of molecular sciences · 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
- Short-term hormonal modulation with mifepristone does not induce oncogenic changes in the endometrium of BRCA1/2 pathogenic variant carriers.Communications medicine · 2026Article
- Dienogest use and the risk of breast and gynecologic cancers: A nationwide population-based study.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 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
- Sex hormones and immune regulation in ovarian cancer.Discover oncology · 2024Review
- Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer.Endocrinology · 2024Article
- DREAM On, DREAM Off: A Review of the Estrogen Paradox in Luminal A Breast Cancers.Biomedicines · 2024Review
- Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients.Journal of experimental & clinical cancer research : CR · 2024Review
- Reevaluating the Role of Progesterone in Ovarian Cancer: Is Progesterone Always Protective?Endocrine reviews · 2023Article
- Hormone Receptors and Epithelial Ovarian Cancer: Recent Advances in Biology and Treatment Options.Biomedicines · 2023Review
- Search for New Participants in the Pathogenesis of High-Grade Serous Ovarian Cancer with the Potential to Be Used as Diagnostic Molecules.Life (Basel, Switzerland) · 2022Article
- DREAM, a possible answer to the estrogen paradox of the Women's Health Initiative Trial.Heliyon · 2022Article
- Progesterone Receptors Promote Quiescence and Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models.The Journal of clinical endocrinology and metabolism · 2021Article
- Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
contextThe ability of ovarian steroids to modify ovarian cancer (OC) risk remains controversial. Progesterone is considered to be protective; recent studies indicate no effect or enhanced OC risk. Knowledge of progesterone receptor (PR) signaling during altered physiology that typifies OC development is limited.
objectiveThis study defines PR-driven oncogenic signaling mechanisms in p53-mutant human fallopian tube epithelia (hFTE), a precursor of the most aggressive OC subtype.
methodsPR expression in clinical samples of serous tubal intraepithelial carcinoma (STIC) lesions and high-grade serous OC (HGSC) tumors was analyzed. Novel PR-A and PR-B isoform-expressing hFTE models were characterized for gene expression and cell cycle progression, emboli formation, and invasion. PR regulation of the DREAM quiescence complex and DYRK1 kinases was established.
resultsSTICs and HGSC express abundant activated phospho-PR. Progestin promoted reversible hFTE cell cycle arrest, spheroid formation, and invasion. RNAseq/biochemical studies revealed potent ligand-independent/-dependent PR actions, progestin-induced regulation of the DREAM quiescence complex, and cell cycle target genes through enhanced complex formation and chromatin recruitment. Disruption of DREAM/DYRK1s by pharmacological inhibition, HPV E6/E7 expression, or DYRK1A/B depletion blocked progestin-induced cell arrest and attenuated PR-driven gene expression and associated OC phenotypes.
conclusionActivated PRs support quiescence and pro-survival/pro-dissemination cell behaviors that may contribute to early HGSC progression. Our data support an alternative perspective on the tenet that progesterone always confers protection against OC. STICs can reside undetected for decades prior to invasive disease; our studies reveal clinical opportunities to prevent the ultimate development of HGSC by targeting PRs, DREAM, and/or DYRKs.
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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.