High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma
High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma
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DOI：
10.1038/sj.onc.1203358
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发表时间：
2000-02-03
期刊：
影响因子：
8
通讯作者：
Nakagawara, A
中科院分区：
文献类型：
--
作者：
Islam, A;Kageyama, H;Nakagawara, A
Survivin（SVV）是凋亡抑制蛋白家族成员，其表达受细胞周期调控。该基因定位于染色体17 q25，该区域经常在神经母细胞瘤（NBL）的晚期获得。然而，SVV在NBL中的作用知之甚少。我们研究了SVV在NBL中的临床和生物学作用。一个1.9 kb的SVV转录本在所有9个NBL细胞系中的表达水平高于成人癌细胞系。在34例原发性NBL中，高水平SVV表达与年龄大于12个月（双样本t检验：P = 0.0003）、晚期（P = 0.0136）、散发性肿瘤（P = 0.0027）和低水平TrkA表达（P = 0.0030）显著相关。在NBL细胞系中，经全反式维甲酸（RA）或血清剥夺处理后，发生凋亡的CHP 134和IMR 32细胞中SVV mRNA表达显著下调，（SH-SY 5 Y和CHP 901）进行RA诱导的分化。另一方面，在增殖的NBL细胞或RA处理的RA难治的SK-N-AS系中，SVVmRNA保持在稳态水平或更确切地说上调。SVV基因转染CHP 134细胞后，可显著抑制RA诱导的细胞凋亡。以上结果提示SVV基因的高表达是晚期神经母细胞瘤的一个强预后指标，可能是17 q基因获得的候选基因之一。
Survivin (SVV) is a family member of inhibitor of apoptosis proteins (IAPs) and its expression is cell cycle regulated. The gene is mapped to chromosome 17q25, the region of which is frequently gained in advanced stages of neuroblastoma (NBL). However, the role of SVV in NBL is poorly understood. Here we studied the clinical and biological role of SVV in NBL. A 1.9 kb SVV transcript was expressed in all of 9 NBL cell lines at higher levels than those in adult cancer cell lines. In 34 primary NBLs, high levels of SVV expression was significantly associated with age greater than 12 months (two sample t-test: P = 0.0003), advanced stages (P = 0.0136), sporadic tumors (P = 0.0027) and low levels of TrkA expression (P = 0.0030). In NBL cell lines, SVV mRNA expression was dramatically down-regulated in CHP134 and IMR32 cells undergoing apoptosis after treatment with all-tr mls retinoic acid (RA) or serum deprivation, It was only moderately decreased in cells (SH-SY5Y and CHP901) undergoing RA-induced differentiation, On the other hand, in proliferating NBL cells or RA-treated SK-N-AS line which is refractory to RA, the SVV mRNA remained at steady state levels or rather up-regulated. Furthermore, transfection of SVV into CHP134 cells induced remarkable inhibition of the RA-induced apoptosis, Collectively, our results suggest that high expression of SVV is a strong prognostic indicator for the advanced stage neuroblastomas, and that it could be one of the candidate genes for the 17q gain.