Modulation of N-myc expression alters the invasiveness of neuroblastoma.
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.
Goodman
L A
LA
Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA.
Liu
B C
BC
Thiele
C J
CJ
Schmidt
M L
ML
Cohn
S L
SL
Yamashiro
J M
JM
Pai
D S
DS
Ikegaki
N
N
Wada
R K
RK
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
D016271:Proto-Oncogene Proteins c-myc