Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma

作者：Lee S G; Jeon H Y; Su Z Z; Richards J E; Vozhilla N; Sarkar D; Van Maerken T; Fisher P B^*

来源：Oncogene, 2009, 28(26): 2476-2484.

DOI：10.1038/onc.2009.93

• neuroblastoma
• AEG-1
• MYCN
• PI3K
• Akt

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 (2009) 28, 2476-2484; doi:10.1038/onc.2009.93; published online 18 May 2009

• 出版日期2009-7