ArticleOncotarget2016
Downregulation of cyclin D1 sensitizes cancer cells to MDM2 antagonist Nutlin-3.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Oncogenic Functions of Alternatively SplicedInternational journal of molecular sciences · 2024Article
- Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers andJCO precision oncology · 2024Article
- Combination Therapy With MDM2 and MEK Inhibitors Is Effective in Patient-Derived Models of Lung Adenocarcinoma With Concurrent Oncogenic Drivers and MDM2 Amplification.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings.Biomedicines · 2023Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- A narrative review of multiple mechanisms of progranulin in cancer: a potential target for anti-cancer therapy.Translational cancer research · 2021Review
- AXL Inactivation Inhibits Mesothelioma Growth and Migration via Regulation of p53 Expression.Cancers · 2020Article
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- CDK4 inhibition diminishes p53 activation by MDM2 antagonists.Cell death & disease · 2018Article
- Correlation of gene expression and associated mutation profiles of APOBEC3A, APOBEC3B, REV1, UNG, and FHIT with chemosensitivity of cancer cell lines to drug treatment.Human genomics · 2018Article
- Synergistic effect of nutlin-3 combined with aspirin in hepatocellular carcinoma HepG2 cells through activation of Bcl-2/Bax signaling pathway.Molecular medicine reports · 2018Article
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Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The MDM2-p53 pathway has a prominent oncogenic function in the pathogenesis of various cancers. Nutlin-3, a small-molecule antagonist of MDM2-p53 interaction, inhibits proliferation in cancer cells with wild-type p53. Herein, we evaluate the expression of MDM2, both the full length and a splicing variant MDM2-A, and the sensitivity of Nutlin-3 in different cancer cell lines. Included are seven cell lines with wild-type p53 (four mesothelioma, one breast cancer, one chondrosarcoma, and one leiomyosarcoma), two liposarcoma cell lines harboring MDM2 amplification and wild-type p53, and one mesothelioma cell line harboring a p53 point mutation. Nutlin-3 treatment increased expression of cyclin D1, MDM2, and p53 in cell lines with wild-type p53. Additive effects were observed in cells containing wild-type p53 through coordinated attack on MDM2-p53 binding and cyclin D1 by lentivirual shRNA knockdown or small molecule inhibition, as demonstrated by immunoblots and cell viability analyses. Further results demonstrate that MDM2 binds to cyclin D1, and that an increase in cyclin D1 expression after Nutlin-3 treatment is correlated with expression and ubiquitin E3-ligase activity of MDM2. MDM2 and p53 knockdown experiments demonstrated inhibition of cyclin D1 by MDM2 but not p53. These results indicate that combination inhibition of cyclin D1 and MDM2-p53 binding warrants clinical evaluation as a novel therapeutic strategy in cancer cells harboring wild-type p53.
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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.