MODULATION OF N-MYC EXPRESSION ALTERS THE INVASIVENESS OF NEUROBLASTOMA

N-myc oncogene expression plays a pivotal role in the biology of neuro blastoma, a common childhood tumor. High N-myc expression is associate d with advanced disease stage, and in animal models, increased express ion results in increased metastatic potential, In normal embryologic d evelopment, N-myc expression is associated with neuroblast migration o ut from the neural crest, To further define the relationship between N -myc and metastasis, an in vitro assay was adapted to measure tumor ce ll 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 clon es, These lines have been characterized previously, and have a decreas e in N-myc expression, growth rate, and tumorigenicity relative to the parent line and vector-only control transfectant, Decrease in N-myc e xpression resulted in a non-proportional increase of tumor cell attach ment, and a proportional decrease in both tumor cell motility and prot eolytic ability, In further experiments, assay of a N-myc-amplified ov erexpressing cell line with an intrinsic heterogeneous pattern of expr ession demonstrated that motile cells expressed higher amounts of N-my c relative to the general population, Together these relationships ind icate 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.