Abstract
Neuroblastoma, derived from neural crest progenitor cells, is the most common extracranial solid tumor of childhood. Astrocyte elevated gene-1 (AEG-1) is a primary mediator of tumor progression and metastasis in several human cancers. In this study, we investigated the potential contribution of AEG-1 in human neuroblastoma pathogenesis. AEG-1 expression was significantly elevated in neuroblastoma patient-derived samples and neuroblastoma cell lines as compared with normal peripheral nerve tissues, normal astrocytes and immortalized melanocytes. Knockdown of AEG-1 by small interfering RNA reduced the tumorigenic properties of highly aggressive neuroblastoma cells. Conversely, over-expression of AEG-1 enhanced proliferation and expression of the transformed state in less aggressive neuroblastoma cells through activation of the phosphatidylinositol 3-kinase-Akt-signaling pathway and stabilization of MYCN. These provocative results indicate that AEG-1 may play a crucial role in the pathogenesis of neuroblastoma and could represent a potential target for therapeutic intervention.
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Abbreviations
- AEG-1:
-
astrocyte elevated gene-1
- AEG-1–7 and AEG-1–8:
-
Tet21N clone 7 and 8 stably expressing AEG-1
- AEG1si:
-
BE(2)-C cells stably expressing AEG-1 siRNA
- Dox:
-
doxycycline
- FBS:
-
fetal bovine serum
- GSK:
-
glycogen synthase kinase
- LY:
-
LY294002
- NCsi:
-
BE(2)-C cells stably expressing negative control siRNA
- NF-κB:
-
nuclear factor-κB
- PC:
-
Tet21N cells stably transfected with pcDNA3.1/Zeo
- PHFA:
-
primary human fetal astrocytes
- PI3K:
-
phosphatidylinositol 3-kinase
- s.d.:
-
standard deviation
- s.e.m.:
-
standard error of mean
- WT:
-
Wortmannin
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Acknowledgements
We thank Drs Manfred Schwab and Frank Westermann (German Cancer Research Center, Heidelberg, Germany) for Tet21N cell line. This study was supported by the National Institutes of Health, NCI Grant R01 CA035675 and NS Grant P01 NS31492, the Samuel Waxman Cancer Research Foundation, the Dana Foundation and the Goldhirsh Foundation. DS is a Harrison Endowed Scholar in Cancer Research. PB Fisher holds the Thelma Newmeyer Corman Chair in Cancer Research and is a SWCRF Investigator.
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Lee, SG., Jeon, HY., Su, ZZ. et al. Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma. Oncogene 28, 2476–2484 (2009). https://doi.org/10.1038/onc.2009.93
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DOI: https://doi.org/10.1038/onc.2009.93
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