ArticlePloS one2016
Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2020Trial
- Discovery of therapeutic targets in cancer using chromatin accessibility and transcriptomic data.Cell systems · 2024Article
- Progesterone inhibits endometrial cancer growth by inhibiting glutamine metabolism through ASCT2.Bioscience reports · 2024Article
- Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.The Journal of steroid biochemistry and molecular biology · 2023Article
- Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma-An Unexpected Correlation to Guide Future Treatment?International journal of molecular sciences · 2023Article
- Comparative- and network-based proteomic analysis of bacterial chondronecrosis with osteomyelitis lesions in broiler's proximal tibiae identifies new molecular signatures of lameness.Scientific reports · 2023Article
- Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer.Cancers · 2022Article
- Sumoylation of Cas9 at lysine 848 regulates protein stability and DNA binding.Life science alliance · 2022Article
- Enhancing progestin therapy via HDAC inhibitors in endometrial cancer.American journal of cancer research · 2022Article
- Incentive Nursing can Effectively Improve the ESCA Level of Patients with Endometrial Cancer after Laparoscopic Hysterectomy.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Multiomics profiling of the expression and prognosis of MCMs in endometrial carcinoma.Bioscience reports · 2021Article
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
- Progesterone stimulates histone citrullination to increase IGFBP1 expression in uterine cells.Reproduction (Cambridge, England) · 2021Article
- IL-37bΔ1-45 suppresses the migration and invasion of endometrial cancer cells by targeting the Rac1/NF-κB/MMP2 signal pathway.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications.International journal of molecular sciences · 2021Review
- 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
- Progesterone receptor inhibits the proliferation and invasion of endometrial cancer cells by up regulating Krüppel-like factor 9.Translational cancer research · 2020Article
- Loss of progesterone receptor through epigenetic regulation is associated with poor prognosis in solid tumors.American journal of cancer research · 2020Article
- MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits Fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy.Gynecologic oncology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR). However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term "molecularly enhanced progestin therapy." What remained unclear was the mechanism of action and if estrogen receptor α (ERα), the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERα at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi) was sufficient to restore functional PR expression, even in cells devoid of ERα. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data reveal a previously unanticipated inverse relationship between the tumor suppressor PR and the oncogene Myc in endometrial cancer.
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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.