ArticleNeoplasia (New York, N.Y.)2009
Mdm2 deficiency suppresses MYCN-Driven neuroblastoma tumorigenesis in vivo.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- Review
- Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- TP53 and TP53-associated genes are correlated with the prognosis of paediatric neuroblastoma.BMC genomic data · 2022Article
- From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma.Journal of personalized medicine · 2021Review
- Venetoclax-based Rational Combinations are Effective in Models ofMolecular cancer therapeutics · 2021Article
- MYCN Function in Neuroblastoma Development.Frontiers in oncology · 2020Review
- Molecularly Targeted Therapy for Neuroblastoma.Children (Basel, Switzerland) · 2018Review
- Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma.Oncotarget · 2018Article
- Article
- Combined ALK and MDM2 inhibition increases antitumor activity and overcomes resistance in humaneLife · 2017Article
- Neuroblastoma treatment in the post-genomic era.Journal of biomedical science · 2017Review
- Article
- Neuroblastoma: molecular pathogenesis and therapy.Annual review of medicine · 2015Review
- Mechanisms of neuroblastoma regression.Nature reviews. Clinical oncology · 2014Review
- G-CSF receptor positive neuroblastoma subpopulations are enriched in chemotherapy-resistant or relapsed tumors and are highly tumorigenic.Cancer research · 2013Article
- Cell survival signaling in neuroblastoma.Anti-cancer agents in medicinal chemistry · 2013Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma is derived from neural crest precursor components of the peripheral sympathetic nervous system and accounts for more than 15% of all pediatric cancer deaths. A clearer understanding of the molecular basis of neuroblastoma is required for novel therapeutic approaches to improve morbidity and mortality. Neuroblastoma is uniformly p53 wild type at diagnosis and must overcome p53-mediated tumor suppression during pathogenesis. Amplification of the MYCN oncogene correlates with the most clinically aggressive form of the cancer, and MDM2, a primary inhibitor of the p53 tumor suppressor, is a direct transcriptional target of, and positively regulated by, both MYCN and MYCC. We hypothesize that MDM2 contributes to MYCN-driven tumorigenesis helping to ameliorate p53-dependent apoptotic oncogenic stress during tumor initiation and progression. To study the interaction of MYCN and MDM2, we generated an Mdm2 haploinsufficient transgenic animal model of neuroblastoma. In Mdm2(+/-)MYCN transgenics, tumor latency and animal survival are remarkably extended, whereas tumor incidence and growth are reduced. Analysis of the Mdm2/p53 pathway reveals remarkable p53 stabilization counter-balanced by epigenetic silencing of the p19(Arf) gene in the Mdm2 haploinsufficient tumors. In human neuroblastoma xenograft models, conditional small interfering RNA-mediated knockdown of MDM2 in cells expressing wild-type p53 dramatically suppresses tumor growth in a p53-dependent manner. In summary, we provided evidence for a crucial role for direct inhibition of p53 by MDM2 and suppression of the p19(ARF)/p53 axis in neuroblastoma tumorigenesis, supporting the development of therapies targeting these pathways.
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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.