Reference - Detail
| RRC ID | 44203 |
|---|---|
| Author | Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K, Onishi A, Nakamura Y, Kadomatsu K. |
| Title | Midkine promotes neuroblastoma through Notch2 signaling. |
| Journal | Cancer Res |
| Abstract |
Midkine is a heparin-binding growth factor highly expressed in various cancers, including neuroblastoma, the most common extracranial pediatric solid tumor. Prognosis of patients with neuroblastoma in which MYCN is amplified remains particularly poor. In this study, we used a MYCN transgenic model for neuroblastoma in which midkine is highly expressed in precancerous lesions of sympathetic ganglia. Genetic ablation of midkine in this model delayed tumor formation and reduced tumor incidence. Furthermore, an RNA aptamer that specifically bound midkine suppressed the growth of neuroblastoma cells in vitro and in vivo in tumor xenografts. In precancerous lesions, midkine-deficient MYCN transgenic mice exhibited defects in activation of Notch2, a candidate midkine receptor, and expression of the Notch target gene HES1. Similarly, RNA aptamer-treated tumor xenografts also showed attenuation of Notch2-HES1 signaling. Our findings establish a critical role for the midkine-Notch2 signaling axis in neuroblastoma tumorigenesis, which implicates new strategies to treat neuroblastoma. |
| Volume | 73(4) |
| Pages | 1318-27 |
| Published | 2013-2-15 |
| DOI | 10.1158/0008-5472.CAN-12-3070 |
| PII | 0008-5472.CAN-12-3070 |
| PMID | 23243020 |
| MeSH | Animals Aptamers, Nucleotide / genetics Aptamers, Nucleotide / metabolism Aptamers, Nucleotide / pharmacology Blotting, Western Cell Line, Tumor Cytokines / genetics* Cytokines / metabolism Ganglia, Sympathetic / metabolism Ganglia, Sympathetic / pathology Gene Expression Regulation, Neoplastic HEK293 Cells Humans Immunohistochemistry Mice Mice, 129 Strain Mice, Knockout Mice, Nude Mice, Transgenic Midkine Neuroblastoma / genetics* Neuroblastoma / pathology Neuroblastoma / prevention & control Protein Binding Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism Receptor, Notch2 / genetics* Receptor, Notch2 / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* Xenograft Model Antitumor Assays |
| IF | 9.727 |
| Times Cited | 28 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | LNCap.FGC(RCB2144) |