Modulation of N-myc expression alters the invasiveness of neuroblastoma

Clin Exp Metastasis. 1997 Mar;15(2):130-9. doi: 10.1023/a:1018448710006.


N-myc oncogene expression plays a pivotal role in the biology of neuroblastoma, a common childhood tumor. High N-myc expression is associated with advanced disease stage, and in animal models, increased expression results in increased metastatic potential. In normal embryologic development, N-myc expression is associated with neuroblast migration out from the neural crest. To further define the relationship between N-myc and metastasis, an in vitro assay was adapted to measure tumor cell attachment, motility, and proteolytic ability in neuroblastoma cell lines. These parameters were examined in a non-amplified, uniformly N-myc overexpressing cell line and its anti-sense N-myc expressing clones. These lines have been characterized previously, and have a decrease in N-myc expression, growth rate, and tumorigenicity relative to the parent line and vector-only control transfectant. Decrease in N-myc expression resulted in a non-proportional increase of tumor cell attachment, and a proportional decrease in both tumor cell motility and proteolytic ability. In further experiments, assay of a N-myc-amplified overexpressing cell line with an intrinsic heterogeneous pattern of expression demonstrated that motile cells expressed higher amounts of N-myc relative to the general population. Together these relationships indicate that N-myc plays a causative role in the invasive phenotype, and suggest that metastasis may, in part, result from the disruption of a developmentally important normal process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Adhesion
  • Cell Movement
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc / physiology*
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neuroblastoma / genetics*
  • Neuroblastoma / secondary*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Tumor Cells, Cultured


  • Proto-Oncogene Proteins c-myc