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PMID:12545161
| Citation |
Wiedemeyer, R, Westermann, F, Wittke, I, Nowock, J and Schwab, M (2003) Ataxin-2 promotes apoptosis of human neuroblastoma cells. Oncogene 22:401-11 |
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| Abstract |
Neuroblastoma is a highly heterogeneous tumor of young children. Although many advances have been made towards understanding the molecular mechanisms dictating the phenotypic heterogeneity, the prognosis of children with neuroblastoma, particularly of progressively growing variants, has remained dire. About 10% of neuroblastomas regress spontaneously, probably by apoptosis, while another 20% have amplified the MYCN gene resulting in a poor prognosis. In pursuit of identifying cell death-associated genes in neuroblastoma, we encountered the SCA2 gene, coding for ataxin-2, as an important player. Here, we report that enforced expression of wild-type ataxin-2, but not of mutant ataxin-2, sensitizes neuroblastoma cells for apoptosis. In line with this, higher levels of ataxin-2 were detected in apoptotic cells compared to nonapoptotic cells. Neuroblastoma tumors with amplified MYCN contain significantly less ataxin-2 protein than tumors without amplified MYCN. Collectively, our data suggest that ataxin-2 has an important role in regulating the susceptibility of neuroblastoma cells to apoptotic stimuli in vitro and in vivo. |
| Links |
PubMed Online version:10.1038/sj.onc.1206150 |
| Keywords |
Amino Acid Chloromethyl Ketones/pharmacology; Apoptosis/physiology; Caspases/antagonists & inhibitors; Caspases/metabolism; Cysteine Proteinase Inhibitors/pharmacology; Enzyme Activation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Mutation; Nerve Tissue Proteins; Neuroblastoma/drug therapy; Neuroblastoma/genetics; Neuroblastoma/pathology; Nuclear Proteins/genetics; Oncogene Proteins/genetics; Peptides/genetics; Proteins/genetics; Proteins/metabolism; Tumor Cells, Cultured; Up-Regulation |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
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