ArticleOncotarget2014
Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 47 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
- Construction and initial validation of key gene network for progesterone resistance in endometrial cancer based on genome-wide CRISPR screening.Scientific reports · 2026Article
- Molecular classification of endometrial cancer in fertility-sparing-treatment: toward a personalized clinical approach.Frontiers in oncology · 2026Review
- Oxidative stress-mediated responses in endometrial cancer cells: contrasting effects of doxorubicin and menadione.Frontiers in physiology · 2026Article
- Advances in the molecular mechanisms underlying progestin resistance in endometrial cancer.Fundamental research · 2025Review
- Epigenetic Therapies in Endocrine-Related Cancers: Past Insights and Clinical Progress.Cancers · 2025Review
- Dual PI3K and HDAC inhibitor, CUDC-907, effectively inhibits endometrial cancer growthFrontiers in oncology · 2025Article
- The Dual Faces of Oestrogen: The Impact of Exogenous Oestrogen on the Physiological and Pathophysiological Functions of Tissues and Organs.International journal of molecular sciences · 2024Review
- Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.The Journal of steroid biochemistry and molecular biology · 2023Article
- Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma.Cancers · 2022Review
- Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer.Cancers · 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
- Enhancing progestin therapy via HDAC inhibitors in endometrial cancer.American journal of cancer research · 2022Article
- The effect of pre-analytical variables on downstream application and data analysis of human endometrial biopsies.Human reproduction open · 2022Article
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
- Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications.International journal of molecular sciences · 2021Review
- Histone acetylation and the role of histone deacetylases in normal cyclic endometrium.Reproductive biology and endocrinology : RB&E · 2020Review
- Loss of progesterone receptor through epigenetic regulation is associated with poor prognosis in solid tumors.American journal of cancer research · 2020Article
- DNMT3A/3B overexpression might be correlated with poor patient survival, hypermethylation and low expression of ESR1/PGR in endometrioid carcinoma: an analysis of The Cancer Genome Atlas.Chinese medical journal · 2019Article
- The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer.Cancer biology & therapy · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledProgesterone, acting through its receptor, PR (progesterone receptor), is the natural inhibitor of uterine endometrial carcinogenesis by inducing differentiation. PR is downregulated in more advanced cases of endometrial cancer, thereby limiting the effectiveness of hormonal therapy. Our objective was to understand and reverse the mechanisms underlying loss of PR expression in order to improve therapeutic outcomes. Using endometrial cancer cell lines and data from The Cancer Genome Atlas, our findings demonstrate that PR expression is downregulated at four distinct levels. In well-differentiated cancers, ligand-induced receptor activation and downregulation are intact. miRNAs mediate fine tuning of PR levels. As differentiation is lost, PR silencing is primarily at the epigenetic level. Initially, recruitment of the polycomb repressor complex 2 to the PR promoter suppresses transcription. Subsequently, DNA methylation prevents PR expression. Appropriate epigenetic modulators reverse these mechanisms. These data provide a rationale for combining epigenetic modulators with progestins as a therapeutic strategy for endometrial cancer. SIGNIFICANCE: Traditional hormonal therapy for women with endometrial cancer can be molecularly enhanced by combining progestins with epigenetic modulators, thereby increasing progesterone receptor expression and significantly improving treatment efficacy.
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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.