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The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2

Oncogene volume 21, pages 2097–2101 (2002)Cite this article

Abstract

Gain of chromosome 17q material is the most frequent genetic abnormality in neuroblastomas. The common region of gain is at least 375 cR large, which has precluded the identification of genes with a role in neuroblastoma pathogenesis. Neuroblastoma also frequently show amplification of the N-myc oncogene, which correlates closely with 17q gain. Both events are strong predictors of unfavorable prognosis. To identify genes that are part of the N-myc downstream pathway, we constructed SAGE libraries of an N-myc transfected and a control cell line. This identified the chromosome 17q genes nm23-H1 and nm23-H2 as being 6–10 times induced in the N-myc expressing cells. Northern and Western blot analysis confirmed this up-regulation. Time-course experiment shows that both genes are induced within 4 h after N-myc is switched on. Furthermore, we demonstrate also that c-myc can up-regulate nm23-H1 and nm23-H2 expression. Neuroblastoma tumor and cell line panels reveal a striking correlation between N-myc amplification and mRNA and protein expression of both nm23 genes. We show that the nm23 genes are located at the edge of the common region of chromosome 17q gain previously described in neuroblastoma cell lines. Our findings suggest that nm23-H1 and nm23-H2 expression is increased by 17q gain in neuroblastoma and can be further up-regulated by myc overexpression. These observations suggest a major role for nm23-H1 and nm23-H2 in tumorigenesis of unfavorable neuroblastomas.

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Acknowledgements

We thank ML Lacombe for providing the NM23-H1 and H2 antibodies. This research was supported by grants from the Dutch Cancer Society (AMC97-1461), the Stichting Kindergeneeskundig Kankeronderzoek. HN Caron is a research fellow of The Royal Netherlands Academy of Arts and Sciences (KNAW).

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Author notes

  1. Kathy Boon

    Present address: Department of Pathology, Duke University Medical Center, Durham, 27710, NC, USA

Authors and Affiliations

  1. Department of Human Genetics, Academic Medical Center, University of Amsterdam, PO box 22700, Amsterdam, 1100, DE, The Netherlands

    Marc B Godfried, Monique Veenstra, Peter v Sluis, Ronald v Asperen, Marie Christien Hermus, Barbara DC v Schaik, Rogier Versteeg & Huib N Caron

  2. Bioinformatics Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Barbara DC v Schaik

  3. Department of Pediatric Oncology and Hematology, Emma Kinderziekenhuis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Tom PA Voûte & Huib N Caron

  4. DKFZ, Heidelberg, Berlin, Germany

    Manfred Schwab

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Correspondence to Huib N Caron.

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Godfried, M., Veenstra, M., v Sluis, P. et al. The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2. Oncogene 21, 2097–2101 (2002). https://doi.org/10.1038/sj.onc.1205259

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