ArticleOncotarget2016
MDM2 is a potential therapeutic target and prognostic factor for ovarian clear cell carcinomas with wild type TP53.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Article
- Comprehensive analysis of consensus molecular subtypes for ovarian cancer from bulk to single-cell perspectives.The Journal of biological chemistry · 2024Article
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Article
- Article
- Discovery and development of botanical natural products and their analogues as therapeutics for ovarian cancer.Natural product reports · 2023Review
- Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR.Journal of ovarian research · 2023Article
- MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis.Cancer research · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Alpha Mangostin and Cisplatin as Modulators of Exosomal Interaction of Ovarian Cancer Cell with Fibroblasts.International journal of molecular sciences · 2022Article
- Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma.Nature communications · 2022Article
- Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas.Cancers · 2021Review
- Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.International journal of molecular sciences · 2021Review
- Changes in SLIT2 expression are associated with the migration of human ovarian clear cell carcinoma cells.Oncology letters · 2021Article
- Cellular Mechanism of Gene Mutations and Potential Therapeutic Targets in Ovarian Cancer.Cancer management and research · 2021Review
- Research Progress in Prognostic Factors and Biomarkers of Ovarian Cancer.Journal of Cancer · 2021Review
- A single institutional experience treating adipocytic tumors: incidence, disease-related outcomes, and the clinical significance of MDM2 analysis.Orthopedic reviews · 2020Article
- Effect of murine double-minute 2 inhibitors in preclinical models of advanced clear cell carcinomas originating from ovaries and kidneys.Cancer science · 2020Article
- Morphological and molecular heterogeneity of epithelial ovarian cancer: Therapeutic implications.EJC supplements : EJC : official journal of EORTC, European Organization for Research and Treatment of Cancer ... [et al.] · 2020Article
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MDM2, a ubiquitin ligase, suppresses wild type TP53 via proteasome-mediated degradation. We evaluated the prognostic and therapeutic value of MDM2 in ovarian clear cell carcinoma. MDM2 expression in ovarian cancer tissues was analyzed by microarray and real-time PCR, and its relationship with prognosis was evaluated by Kaplan-Meier method and log-rank test. The anti-tumor activities of MDM2 siRNA and the MDM2 inhibitor RG7112 were assessed by cell viability assay, western blotting, and flow cytometry. The anti-tumor effects of RG7112 in vivo were examined in a mouse xenograft model. MDM2 expression was significantly higher in clear cell carcinoma than in ovarian high-grade serous carcinoma (P = 0.0092) and normal tissues (P = 0.035). High MDM2 expression determined by microarray was significantly associated with poor progression-free survival and poor overall survival (P = 0.0002, and P = 0.0008, respectively). Notably, RG7112 significantly suppressed cell viability in clear cell carcinoma cell lines with wild type TP53. RG7112 also strongly induced apoptosis, increased TP53 phosphorylation, and stimulated expression of the proapoptotic protein PUMA. Similarly, siRNA knockdown of MDM2 induced apoptosis. Finally, RG7112 significantly reduced the tumor volume of xenografted RMG-I clear cell carcinoma cells (P = 0.033), and the density of microvessels (P = 0.011). Our results highlight the prognostic value of MDM2 expression in clear cell carcinoma. Thus, MDM2 inhibitors such as RG7112 may constitute a class of potential therapeutics.
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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.