Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma.
Oncogene. 2009 May 18;
Authors: Lee SG, Jeon HY, Su ZZ, Richards JE, Vozhilla N, Sarkar D, Van Maerken T, Fisher PB
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.Oncogene advance online publication, 18 May 2009; doi:10.1038/onc.2009.93.
PMID: 19448665 [PubMed - as supplied by publisher]