Restoration of promyelocytic leukemia protein-nuclear bodies in neuroblastoma cells enhances retinoic acid responsiveness.
Restoration of promyelocytic leukemia protein-nuclear bodies in neuroblastoma cells enhances retinoic acid responsiveness.
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神经母细胞瘤细胞中早幼粒细胞白血病蛋白核体的恢复增强了视黄酸反应性。
DOI：
10.1158/0008-5472.can-03-1199
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发表时间：
2004
期刊：
影响因子：
11.2
通讯作者：
Bloch,DonaldB
中科院分区：
文献类型：
--
作者：
Yu,JiangHong;Nakajima,Ayako;Nakajima,Hiroshi;Diller,LisaR;Bloch,KennethD;Bloch,DonaldB
神经母细胞瘤是婴儿期最常见的实体瘤，被认为是由于神经元脊胚胎细胞分化障碍所致。早幼粒细胞白血病蛋白(PML)核体是一种在急性早幼粒细胞白血病发病过程中被破坏的细胞结构，急性早幼粒细胞白血病是一种以髓系细胞分化受损为特征的疾病。在研究PML核体的组成和功能的过程中，我们观察到人神经母细胞瘤细胞系SH-SY5Y缺乏这些结构，PML核体的缺失是N型和I型神经母细胞瘤细胞的特征，而不是S型神经母细胞瘤的特征。5-溴-2‘-脱氧尿苷、全反式维甲酸或干扰素-γ诱导神经母细胞瘤细胞分化诱导核体形成。在未分化的神经母细胞瘤组织切片中未检测到PML-核小体，但在分化肿瘤的神经母细胞中可检测到。在神经母细胞瘤细胞中表达PML可恢复PML核小体，增强对全反式维甲酸的反应性，并诱导细胞分化。增加PML表达的药物治疗可能被证明是神经母细胞瘤综合治疗的重要组成部分。
Neuroblastoma is the most common solid tumor of infancy and is believed to result from impaired differentiation of neuronal crest embryonal cells. The promyelocytic leukemia protein (PML)-nuclear body is a cellular structure that is disrupted during the pathogenesis of acute promyelocytic leukemia, a disease characterized by impaired myeloid cell differentiation. During the course of studies to examine the composition and function of PML-nuclear bodies, we observed that the human neuroblastoma cell line SH-SY5Y lacked these structures and that the absence of PML-nuclear bodies was a feature of N- and I-type, but not S-type, neuroblastoma cell lines. Induction of neuroblastoma cell differentiation with 5-bromo-2′deoxyuridine, all-trans-retinoic acid, or IFN-γ induced PML-nuclear body formation. PML-nuclear bodies were not detected in tissue sections prepared from undifferentiated neuroblastomas but were present in neuroblasts in differentiating tumors. Expression of PML in neuroblastoma cells restored PML-nuclear bodies, enhanced responsiveness to all-trans-retinoic acid, and induced cellular differentiation. Pharmacological therapies that increase PML expression may prove to be important components of combined modalities for the treatment of neuroblastoma.