ArticleCurrent pharmaceutical design2014
Epigenetic modification restores functional PR expression in endometrial cancer cells.
Article in Current pharmaceutical design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 43 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
- MIG-6 Regulates HDAC1-Mediated Angiogenesis and Tumorigenesis in PTEN-Deficient Endometrioid Endometrial Cancer.Molecular cancer research : MCR · 2026Article
- Construction and initial validation of key gene network for progesterone resistance in endometrial cancer based on genome-wide CRISPR screening.Scientific reports · 2026Article
- CRL4International journal of biological sciences · 2026Article
- FOXA2 sensitizes endometrial carcinoma to progestin-mediated conservative therapy by triggering PR transcriptional activation.Oncogene · 2025Article
- 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
- Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.The Journal of steroid biochemistry and molecular biology · 2023Article
- RNA-seq and ATAC-seq analysis of CD163Cancer medicine · 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
- Article
- Enhancing progestin therapy via HDAC inhibitors in endometrial cancer.American journal of cancer research · 2022Article
- Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives.Cancers · 2021Review
- Histone Deacetylase Inhibitors: A Promising Therapeutic Alternative for Endometrial Carcinoma.Disease markers · 2021Review
- Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.Endocrine reviews · 2020Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated tumor. Response to progestin-based therapy correlates positively with progesterone receptor (PR) expression. However, many endometrial tumors have low levels or loss of PR, limiting the clinical application of progestin. We evaluated the ability of epigenetic modulators to restore functional PR expression in Type I endometrial cancer cells with low basal PR. Treatment with the histone deacetylase inhibitor (HDACi) LBH589 induced a profound upregulation of PR mRNA. LBH589 restored PR protein expression at 24 hours and sustained expression for 72 hours, even in the presence of progesterone. LBH589 promoted a dose-dependent increase in PR protein levels, with an obvious increase with 10 nM LBH589. To investigate if the restored PR is functional as a transcription factor, we examined PR nuclear localization and expression of PRE- or Sp1-containing target genes. After treatment with LBH589 in the absence or presence of progesterone, PR nuclear expression was increased as demonstrated by Western blotting of nuclear fractions and immunostaining. Next, restored PR upregulated FoxO1, p21, and p27 and downregulated cyclin D1 in a ligand-dependent manner. Finally, LBH589 treatment induced cell cycle arrest in G1 that was further augmented by progesterone. Regulation of PR target genes was also achieved with other HDAC inhibitors, indicating that agents in this class work similarly with respect to PR. Our findings reveal that epigenetic modulators can restore endogenous functional PR expression in endometrial cancer cells and suggest that strategies to re-establish PR expression will resensitize endometrial tumors to progestin therapy.
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.