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Ataxin-2 promotes apoptosis of human neuroblastoma cells

Oncogene volume 22, pages 401–411 (2003)Cite this article

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.

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Acknowledgements

F Westermann and I Wittke contributed equally to this work. The authors thank Dr D Rudnicki and Prof. G Auburger for pCI-SCA2-CAG22, Prof. PH Krammer for the C15 antibody and the members of the German Neuroblastoma Study Group. This work was supported by Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft, BMBF, Deutsches Humangenomprojekt and the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel's Ministry of Science (MOS).

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Authors and Affiliations

  1. Department of Cytogenetics (H0400), German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, 69121, Germany

    Ruprecht Wiedemeyer, Frank Westermann, Isabel Wittke & Manfred Schwab

  2. Section Molecular Neurogenetics, JW Goethe-Universität, Theodor Stern Kai 7, Frankfurt, 60590, Germany

    Joachim Nowock

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  1. Ruprecht Wiedemeyer
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  2. Frank Westermann
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Correspondence to Manfred Schwab.

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Wiedemeyer, R., Westermann, F., Wittke, I. et al. Ataxin-2 promotes apoptosis of human neuroblastoma cells. Oncogene 22, 401–411 (2003). https://doi.org/10.1038/sj.onc.1206150

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