Girgert R, Wittrock J, Schweizer P
Department of Pediatric Surgery, University of Tübingen, Germany.
Eur J Pediatr Surg. 2001 Dec;11(6):363-7. doi: 10.1055/s-2001-19725.
In neuroblastoma, amplification of the protooncogene N-myc is the most important molecular characteristic predicting a bad outcome for the patients. Despite the importance of the N-myc gene, little is known about the mechanisms regulating its expression. We found evidence that insulin-like growth factor II stimulates the growth of neuroblastoma in a paracrine fashion. Two neuroblastoma cell lines predominantly expressed IGF-II whereas two other cell lines expressed the IGF-receptor. In a receptor-positive cell line, N-myc expression was enhanced by stimulation with IGF-II. As the growth-stimulating signals of the IGF receptor are transmitted via Ras proteins, inactivation of Ras is one promising tool to prevent the induction of N-myc expression by IGF-II. Treatment of neuroblastoma cells with an inhibitor of the farnesyl-protein-transferase (FPTase) inactivated H-ras protein completely and N-ras protein by more than 50 %. Cell growth of neuroblastoma cells in serum containing medium was clearly diminished by inhibition of FPTase. The growth-promoting effect of IGF-II was reduced to exactly half the amount observed in non-inhibited cells.
在神经母细胞瘤中，原癌基因N-myc的扩增是预测患者不良预后的最重要分子特征。尽管N-myc基因很重要，但关于调节其表达的机制却知之甚少。我们发现有证据表明胰岛素样生长因子II以旁分泌方式刺激神经母细胞瘤的生长。两种神经母细胞瘤细胞系主要表达IGF-II，而另外两种细胞系表达IGF受体。在一种受体阳性细胞系中，IGF-II刺激可增强N-myc的表达。由于IGF受体的生长刺激信号通过Ras蛋白传递，Ras失活是防止IGF-II诱导N-myc表达的一种有前景的手段。用法尼基蛋白转移酶（FPTase）抑制剂处理神经母细胞瘤细胞可使H-ras蛋白完全失活，N-ras蛋白失活超过50%。抑制FPTase可明显减少含血清培养基中神经母细胞瘤细胞的生长。IGF-II的促生长作用降低到未抑制细胞中观察到的一半。
