Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma
| Autor: | Zhao-zhong Su, Seok-Geun Lee, J E Richards, Devanand Sarkar, Vozhilla N, Paul B. Fisher, Hyun Yong Jeon, T. Van Maerken |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Biology Mice Neuroblastoma Phosphatidylinositol 3-Kinases Fetus Cell Line Tumor Genetics medicine Animals Humans Peripheral Nerves Progenitor cell neoplasms Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Oncogene Proteins N-Myc Proto-Oncogene Protein Gene knockdown Membrane Proteins Nuclear Proteins RNA-Binding Proteins Neural crest medicine.disease Gene Expression Regulation Neoplastic Cell Transformation Neoplastic medicine.anatomical_structure Tumor progression Astrocytes Gene Knockdown Techniques Immunology Cancer research Melanocytes Neuroglia Cell Adhesion Molecules Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Oncogene. 28:2476-2484 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2009.93 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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