Nakagawara A, Kadomatsu K, Sato S, Kohno K, Takano H, Akazawa K, Nose Y, Kuwano M
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University 60, Fukuoka, Japan.
Cancer Res. 1990 May 15;50(10):3043-7.
Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N-myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression.
N - myc基因的基因组扩增是神经母细胞瘤重要的预后指标。N - myc基因扩增的肿瘤最初对化疗敏感，但常常会产生耐药性，复发，并最终导致患者死亡。我们检测了35例手术切除的神经母细胞瘤在产生耐药性之前以及4例化疗耐药的复发性肿瘤中N - myc基因的扩增和表达情况以及mdr - 1的表达情况。结果发现mdr - 1 mRNA表达与N - myc表达呈负相关。在晚期且组织学上未分化的神经母细胞瘤（即N - myc表达升高的同一组肿瘤）中，mdr - 1基因表达处于低水平。肿瘤mdr - 1表达水平高且N - myc表达水平低的患者预后明显更好。mdr - 1表达增加在神经母细胞瘤获得多药耐药性过程中所起的作用（如果有）仍不清楚。然而，与N - myc扩增和/或表达相关的侵袭性临床行为似乎与mdr - 1表达下调有关。
