Cohn S L, Salwen H, Quasney M W, Ikegaki N, Cowan J M, Herst C V, Kennett R H, Rosen S T, DiGiuseppe J A, Brodeur G M
Department of Pediatrics, Northwestern University Medical Center, Chicago, IL 60614.
Oncogene. 1990 Dec;5(12):1821-7.
Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.
致癌基因N - myc的基因组扩增与神经母细胞瘤（NB）患者的肿瘤快速进展及预后不良相关。然而，40%未发生N - myc扩增的NB在临床上也具有侵袭性。因此，除了N - myc拷贝数之外的其他因素必定在这些NB的肿瘤进展中发挥作用。我们从一名患有快速进展性疾病且未发生N - myc扩增的患者的原发性肿瘤中建立了一种不同寻常的人类NB细胞系（NBL - S）。其体外倍增时间（48小时）以及将2×10⁷个细胞注射到裸鼠体内至可检测到肿瘤的时间（46天）与N - myc扩增的NB细胞系相似。然而，核型分析未发现双微体（DMs）、均匀染色区（HSRs）或1号染色体缺失的证据，这些是NB细胞系中常见的特征。这些细胞具有N - myc扩增的NB典型的细胞表面表型（HLA - A、B、C阴性且HSAN 1.2阳性），并且与其他NB细胞系一样，表达N - myc RNA和蛋白。有趣的是，与之前在N - myc扩增的NB细胞系中描述的较短的N - myc蛋白半衰期（约30分钟）相比，NBL - S中N - myc蛋白的半衰期延长（约100分钟）。由于N - myc蛋白被认为具有调节作用，该蛋白半衰期的延长可能是在未发生N - myc扩增且快速进展的NB中调节生长的一个重要因素。
