title: Modulation of N-myc expression alters the invasiveness of neuroblastoma.
abstract: 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.
authors.affiliation: Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Goodman
authors.forename: B C
authors.initials: BC
authors.lastname: Liu
authors.forename: C J
authors.initials: CJ
authors.lastname: Thiele
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.forename: S L
authors.initials: SL
authors.lastname: Cohn
authors.forename: J M
authors.initials: JM
authors.lastname: Yamashiro
authors.forename: D S
authors.initials: DS
authors.lastname: Pai
authors.forename: N
authors.initials: N
authors.lastname: Ikegaki
authors.forename: R K
authors.initials: RK
authors.lastname: Wada
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000556:secondary*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016271:Proto-Oncogene Proteins c-myc