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Loss of one HuD allele on chromosome #1p selects for amplification of the N-myc proto-oncogene in human neuroblastoma cells

Oncogene volume 25, pages 706–712 (2006)Cite this article

Abstract

In human neuroblastoma tumors, amplification of the N-myc proto-oncogene and loss of all or part of the short arm of chromosome #1 are both associated with a poor prognosis. Accruing evidence indicates that it is the absence of one allele of the HuD (ELAVL4) gene, encoding the neuronal-specific RNA-binding protein HuD and localized to 1p34, that is linked to amplification. In 12 human neuroblastoma cell lines, N-myc amplification correlates with loss of one HuD allele and decreased HuD expression. Transfection experiments demonstrate that modulating HuD expression affects N-myc gene copy number as well as expression. Introduction of a sense HuD construct into two N-myc amplified cell lines considerably increases N-myc expression whereas gene copy number decreases. Conversely, expression of antisense HuD in N-myc nonamplified SH-SY5Y cells reduces HuD and N-myc mRNA levels even as cells show amplification of the N-myc gene. Thus, N-myc gene copy number is modulated by alteration of HuD expression. We propose that haploinsufficiency of HuD due to chromosome #1p deletion in neuroblastoma selects for cells that amplify N-myc genes. Application of these findings could lead to more effective therapies in the treatment of those patients with the worst prognosis.

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Acknowledgements

This research was supported, in part, by grants from the National Cancer Institute (CA77593) and the GRATIS Fund.

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  1. Department of Biological Sciences, Laboratory of Neurobiology, Fordham University, Bronx, NY, USA

    K B Grandinetti, B A Spengler, J L Biedler & R A Ross

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  1. K B Grandinetti
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  2. B A Spengler
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  3. J L Biedler
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  4. R A Ross
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Correspondence to R A Ross.

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Grandinetti, K., Spengler, B., Biedler, J. et al. Loss of one HuD allele on chromosome #1p selects for amplification of the N-myc proto-oncogene in human neuroblastoma cells. Oncogene 25, 706–712 (2006). https://doi.org/10.1038/sj.onc.1209095

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