| RRC ID |
44203
|
| 著者 |
Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K, Onishi A, Nakamura Y, Kadomatsu K.
|
| タイトル |
Midkine promotes neuroblastoma through Notch2 signaling.
|
| ジャーナル |
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.
|
| 巻・号 |
73(4)
|
| ページ |
1318-27
|
| 公開日 |
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
|
| 引用数 |
28
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
LNCap.FGC(RCB2144) |
