Lee S-G, Jeon H-Y, Su Z-Z, Richards J E, Vozhilla N, Sarkar D, Van Maerken T, Fisher P B
Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
Oncogene. 2009 Jul 2;28(26):2476-84. doi: 10.1038/onc.2009.93. Epub 2009 May 18.
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.
神经母细胞瘤起源于神经嵴祖细胞，是儿童最常见的颅外实体瘤。星形胶质细胞上调基因1（AEG-1）是几种人类癌症中肿瘤进展和转移的主要介质。在本研究中，我们调查了AEG-1在人类神经母细胞瘤发病机制中的潜在作用。与正常外周神经组织、正常星形胶质细胞和永生化黑素细胞相比，AEG-1在神经母细胞瘤患者来源的样本和神经母细胞瘤细胞系中的表达显著升高。通过小干扰RNA敲低AEG-1可降低高侵袭性神经母细胞瘤细胞的致瘤特性。相反，AEG-1的过表达通过激活磷脂酰肌醇3-激酶-Akt信号通路和稳定MYCN，增强了低侵袭性神经母细胞瘤细胞的增殖和转化状态的表达。这些引人注目的结果表明，AEG-1可能在神经母细胞瘤的发病机制中起关键作用，并可能成为治疗干预的潜在靶点。
