ArticleCancer research2013
Progesterone receptor signaling in the microenvironment of endometrial cancer influences its response to hormonal therapy.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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.
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Who cites it
47 citing papers in PubMed, 82 citations in OpenAlex.
- A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Molecular Prognosticators Guiding Fertility-Sparing Surgery in Early-Stage Endometrial Cancer: A Comprehensive Review.Cancers · 2025Review
- Progesterone receptor isoform modulation via enhancer activation regulates progesterone signaling in endometrial stromal cells.F&S science · 2025Article
- Multiplexed Imaging Mass Cytometry Reveals Tumor-immune Microenvironment-dependent Hormone Receptor Expression in Adult-Type Ovarian Granulosa Cell Tumors.Cancer research communications · 2025Article
- Advances in the molecular mechanisms underlying progestin resistance in endometrial cancer.Fundamental research · 2025Review
- Epigenetics of Endometrial Cancer: The Role of Chromatin Modifications and Medicolegal Implications.International journal of molecular sciences · 2025Review
- Female sex hormones exacerbate retinal neurodegeneration.Science advances · 2025Article
- SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner.Nature communications · 2025Article
- Article
- Krüppel-like factor 12 decreases progestin sensitivity in endometrial cancer by inhibiting the progesterone receptor signaling pathway.Translational oncology · 2024Article
- Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Unveiling DNA methylation: early diagnosis, risk assessment, and therapy for endometrial cancer.Frontiers in oncology · 2024Review
- Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer.Endocrinology · 2023Review
- RNA-seq and ATAC-seq analysis of CD163Cancer medicine · 2023Article
- MIG-6 Is Critical for Progesterone Responsiveness in Human Complex Atypical Hyperplasia and Early-Stage Endometrial Cancer.International journal of molecular sciences · 2022Article
- Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients.Scientific reports · 2022Article
- MPA alters metabolic phenotype of endometrial cancer-associated fibroblasts from obese women via IRS2 signaling.PloS one · 2022Article
- Adult stem cells in endometrial regeneration: Molecular insights and clinical applications.Molecular reproduction and development · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Progesterone, an agonist for the progesterone receptor (PR), can be an efficacious and well-tolerated treatment in endometrial cancer. The clinical use of progesterone is limited because of the lack of biomarkers that predict hormone sensitivity. Despite its efficacy in cancer therapy, mechanisms and site of action for progesterone remain unknown. Using an in vivo endometrial cancer mouse model driven by clinically relevant genetic changes but dichotomous responses to hormonal therapy, we show that signaling through stromal PR is necessary and sufficient for progesterone antitumor effects. Endometrial cancers resulting from epithelial loss of PTEN (PTENKO) were hormone sensitive and had abundant expression of stromal PR. Stromal deletion of PR as a single genetic change in these tumors induced progesterone resistance indicating that paracrine signaling through the stroma is essential for the progesterone therapeutic effects. A hormone-refractory endometrial tumor with low levels of stromal PR developed when activation of KRAS was coupled with PTEN-loss (PTENKO/Kras). The innate progesterone resistance in PTENKO/Kras tumors stemmed from methylation of PR in the tumor microenvironment. Add-back of stromal PR expressed from a constitutively active promoter sensitized these tumors to progesterone therapy. Results show that signaling through stromal PR is sufficient for inducing hormone responsiveness. Our findings suggest that epigenetic derepression of stromal PR could be a potential therapeutic target for sensitizing hormone-refractory endometrial tumors to progesterone therapy. On the basis of these results, stromal expression of PR may emerge as a reliable biomarker in predicting response to hormonal therapy.
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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.