ArticleAmerican journal of cancer research2020
Loss of progesterone receptor through epigenetic regulation is associated with poor prognosis in solid tumors.
Article in American journal of cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Exosomal-miR-32-5p directly targets FOXN2 to regulate the proliferation, migration and apoptosis of uterine corpus endometrial carcinoma via the PI3K/AKT/BCL-2 pathway.Oncology letters · 2026Article
- EpGAT: integrating epigenetics and 3D genome structure to predict alternative splicing and polyadenylation.Briefings in bioinformatics · 2026Article
- Does immunotherapy hold great promise in endometrial cancer care?Frontiers in immunology · 2026Review
- Sex hormone receptor signaling networks drive pancreatic solid-pseudopapillary neoplasm pathogenesis and therapy.Discover oncology · 2025Review
- Advances in the molecular mechanisms underlying progestin resistance in endometrial cancer.Fundamental research · 2025Review
- Dual PI3K and HDAC inhibitor, CUDC-907, effectively inhibits endometrial cancer growthFrontiers in oncology · 2025Article
- Effects of the Overexpression of Progesterone Receptors on a Precancer p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line.International journal of molecular sciences · 2023Article
- Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma.Cancers · 2022Review
- Maternal soybean genistein on prevention of later-life breast cancer through inherited epigenetic regulations.Carcinogenesis · 2022Article
- Analysis of Secreted Proteins from Prepubertal Ovarian Tissues Exposed In Vitro to Cisplatin and LH.Cells · 2022Article
- Enhancing progestin therapy via HDAC inhibitors in endometrial cancer.American journal of cancer research · 2022Article
- Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3.Cancer management and 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
12 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundHormonal therapy using progestins, acting through the progesterone receptor (PR), is a well-established method to treat uterine endometrial hyperplasia and carcinoma. Recent population studies indicate that progestin exposure significantly reduces the incidence of ovarian, pancreatic and lung cancers in addition to endometrial cancer in women. This unexpected differentiating function of progestin in organs outside of the reproductive system led us to hypothesize that progestins/PR are protective against cancer development and progression in many tumor types.
methodsThe Cancer Genome Atlas, Oncomine and Prognostic Databases were searched to determine the relative expression of PR in tumors from multiple sites, and clinical outcomes linked to PR expression were determined. In addition, mRNA and protein expression were evaluated using real-time PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assay was performed to understand the PR downregulation mechanisms in tumor cells and patient samples. Methylation-specific PCR was conducted to survey the PR methylation status. The Student's t-test were performed to determine significance. Flow cytometry was used to quantify apoptotic cells.
resultsLow PR expression levels were consistently linked to less favorable clinical outcomes in endometrial, pancreatic, ovarian and non-small cell lung cancers. Clinical specimens and cell lines from these cancers demonstrate low levels of PR, and we now report that the mechanism for loss of PR is mediated through epigenetic repression. However, PR silencing can be overcome with epigenetic modulators. Histone deacetylase inhibitor (LBH589) and hypomethylating agent (5-aza-decitabine) restored functional PR expression at both the mRNA and protein levels and promoted marked cell death through induction of apoptosis in the presence of progesterone.
conclusionsOur studies support the possibility that progestin therapy in combination with epigenetic modulators, a concept we term "molecularly enhanced progestin therapy", is an approach worthy of study for malignancies originating from tissues outside of the reproductive tract.
Indexed as
Identifiers
32642294PMC7339273W3041631140What 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.