Modulation of N-myc expression alters the invasiveness of neuroblastoma

Modulation of N-myc expression alters the invasiveness of neuroblastoma
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DOI:
10.1023/a:1018448710006
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发表时间:
1997-03-01
影响因子:
4
通讯作者:
Wada, RK
Wada, RK
中科院分区:
医学3区
文献类型:
--
作者:
Goodman, LA;Liu, BCS;Wada, RK

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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.