Delaune A, Corbière C, Benjelloun F D, Legrand E, Vannier J P, Ripoll C, Vasse M
Groupe de recherche MERCI & IHURBM, Faculté de médecine et pharmacie, Rouen, France.
J Neurochem. 2008 Jan;104(1):89-99. doi: 10.1111/j.1471-4159.2007.05019.x. Epub 2007 Nov 6.
Neuroblastoma is one of the most common cancers in children. Neuroblastoma differentiation is linked to the presence of the promyelocytic leukemia (PML) protein. Retinoic acid, a powerful differentiation-inducer in vitro, is a potent agent for the treatment of neuroblastoma. Using two different human neuroblastoma cell lines, SH-SY5Y and LA-N-5, we show here that PML protein leads to the formation of nuclear bodies (PML-NB) after only 1 h of retinoic acid treatment and that this formation is mediated by the extracellular signal-regulated kinase (ERK) pathway. Inhibition of protein kinase C also leads to formation of PML-NB via the ERK pathway. Both sumoylation and phosphorylation of PML in an ERK-dependent pathway are also required for formation of PML-NB. Finally, we show that PML-NB formation in neuroblastoma cells is associated with neurite outgrowth. These results support the proposal that the formation of PML-NB is correlated with the differentiation of neuroblastoma cells.
神经母细胞瘤是儿童最常见的癌症之一。神经母细胞瘤的分化与早幼粒细胞白血病（PML）蛋白的存在有关。视黄酸是一种强大的体外分化诱导剂，是治疗神经母细胞瘤的有效药物。我们使用两种不同的人类神经母细胞瘤细胞系SH-SY5Y和LA-N-5，在此表明，视黄酸处理仅1小时后，PML蛋白就会导致核体（PML-NB）的形成，并且这种形成是由细胞外信号调节激酶（ERK）途径介导的。蛋白激酶C的抑制也通过ERK途径导致PML-NB的形成。PML-NB的形成还需要在ERK依赖途径中PML的SUMO化和磷酸化。最后，我们表明神经母细胞瘤细胞中PML-NB的形成与神经突生长有关。这些结果支持了PML-NB的形成与神经母细胞瘤细胞分化相关的提议。
