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N-myc augments death and attenuates protective effects of Bcl-2 in trophically stressed neuroblastoma cells

Oncogene volume 27, pages 3424–3434 (2008)Cite this article

Abstract

N-myc has proapoptotic functions, yet it acts as an oncogene in neuroblastoma. Thus, antiapoptotic mechanisms have to be operative in neuroblastoma cells that antagonize the proapoptotic effects of N-myc. We conditionally activated N-myc in SH-EP neuroblastoma cells subjected to the trophic stress of serum or nutrient deprivation while changing the expression of Bcl-2, survivin and FLIPL, antiapoptotic molecules often overexpressed in poor prognosis neuroblastomas. Bcl-2 protected SH-EP cells from death during nutritional deprivation by activating energetically advantageous oxidative phosphorylation. N-myc overrode the metabolic protection provided by Bcl-2-induced oxidative phosphorylation by reestablishing the glycolytic phenotype and attenuated the antiapoptotic effect of Bcl-2 during metabolic stress. Survivin partially antagonized the growth suppressive function of N-myc in SH-EP neuroblastoma cells during serum deprivation whereas FLIPL did not. These findings advance our understanding of the functions of N-myc in neuroblastoma cells.

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Acknowledgements

This work was supported by a grant from the Deutsche Krebshilfe to CB.

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  1. A Ushmorov

    Present address: 3Current address: Department of Physiological Chemistry, University of Ulm, Germany,

Authors and Affiliations

  1. University Children's Hospital, Ulm, Germany

    A Ushmorov, H Knauß, K M Debatin & C Beltinger

  2. Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    M D Hogarty & X Liu

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  1. A Ushmorov
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Correspondence to C Beltinger.

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Ushmorov, A., Hogarty, M., Liu, X. et al. N-myc augments death and attenuates protective effects of Bcl-2 in trophically stressed neuroblastoma cells. Oncogene 27, 3424–3434 (2008). https://doi.org/10.1038/sj.onc.1211017

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