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Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma

Oncogene volume 28, pages 2476–2484 (2009)Cite this article

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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Author notes

  1. S -G Lee and H -Y Jeon: These authors equally contributed to this work.

Authors and Affiliations

  1. Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA

    S -G Lee, H -Y Jeon, Z -Z Su, J E Richards, N Vozhilla, D Sarkar & P B Fisher

  2. VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA

    S -G Lee, D Sarkar & P B Fisher

  3. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium

    T Van Maerken

  4. VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA

    D Sarkar & P B Fisher

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Correspondence to S -G Lee or P B Fisher.

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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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