Matsunaga T, Shirasawa H, Enomoto H, Yoshida H, Iwai J, Tanabe M, Kawamura K, Etoh T, Ohnuma N
Department of Pediatric Surgery, Chiba University, School of Medicine, Japan.
Int J Cancer. 1998 Jun 19;79(3):226-31. doi: 10.1002/(sici)1097-0215(19980619)79:3<226::aid-ijc3>3.0.co;2-r.
Neuroblastomas present a wide variety of clinical and biological behaviors, which are reflected by the heterogeneous expressions of protooncogenes related to the neuronal differentiation and amplification of the N-myc gene. High expression of trk A and Ha-ras in neuroblastomas has been shown to be associated with an excellent patient outcome. We have previously reported that neuron-specific src mRNA was increased in chemically differentiated neuroblastoma cell lines and in clinically observed neuroblastomas without N-myc amplification. In the present study, to clarify both the value of neuronal c-srcN2 expression as a prognostic indicator and the significance of the coexpression of these protooncogenes, we examined the expression of 3 alternatively spliced src, trk A and Ha-ras in neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain reaction (PCR). The results indicate that protooncogene expression in neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc gene was amplified exclusively in tumors with low levels of trk A. Low expression of c-srcN2 and trk A might thus characterize different aggressive phenotypes due to different signal transduction pathways of neural differentiation in neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR should provide information about the biological phenotype of a neuroblastoma within a short period of time after obtaining tumor material.
神经母细胞瘤呈现出广泛多样的临床和生物学行为，这通过与神经元分化相关的原癌基因的异质性表达以及N - myc基因的扩增得以体现。已表明神经母细胞瘤中trk A和Ha - ras的高表达与患者的良好预后相关。我们之前报道过，在化学分化的神经母细胞瘤细胞系以及临床观察到的无N - myc扩增的神经母细胞瘤中，神经元特异性src mRNA有所增加。在本研究中，为了阐明神经元c - srcN2表达作为预后指标的价值以及这些原癌基因共表达的意义，我们通过竞争性RNA聚合酶链反应（PCR）检测了60例患者神经母细胞瘤组织中3种选择性剪接的src、trk A和Ha - ras的表达。结果表明，神经母细胞瘤中原癌基因的表达与c - srcN2和trk A的良好预后相关。N - myc基因仅在trk A水平低的肿瘤中扩增。因此，c - srcN2和trk A的低表达可能由于神经母细胞瘤中神经分化的不同信号转导途径而表征不同的侵袭性表型。通过RNA - PCR对c - srcN2和trk A表达进行联合分析，应能在获取肿瘤材料后的短时间内提供有关神经母细胞瘤生物学表型的信息。
