Expression of survivin in neuroblastoma

背景/目的：诱导或阻止细胞死亡的凋亡因子可能内在地控制某些肿瘤的行为。存活素是最近描述的凋亡抑制蛋白（IAP）家族的成员，其以细胞周期依赖性方式表达，并且在组织学不良的肿瘤中发现。本研究探讨了神经母细胞瘤（NB）肿瘤中存在的几种凋亡因子，包括生存素。通过研究NB与肿瘤和细胞系中的行为和细胞动力学的关系，提供了NB中生存功能的线索。方法：在化疗前的15个NB和相关肿瘤以及3个NB细胞系（NB 7，N810和NB 16）中定量表达一组凋亡因子。Survivin和其他凋亡因子以及原发肿瘤中的N-myc扩增与复发疾病和预后相关。在细胞系中评估增殖率、凋亡测定、细胞周期分析和药物或免疫介导的细胞死亡，并评估细胞周期的变化。 ...更多信息 结果：复发的7例肿瘤均表达Survivin，而缓解的8例肿瘤均不表达Survivin。7例复发肿瘤中4例（57.1%）有N-myc扩增。在治愈的8个肿瘤中。Fas在3例（38%）中表达，TRAIL-R1在6例（75%）中表达，肿瘤坏死因子（TNF）-R1在8例（100%）中表达，而这些促凋亡受体分别仅存在于7例继续复发的肿瘤中的1例（14%）、1例（14%）和4例（57%）。在3种细胞系中，NB 10表达最少的生存素，显示最低的增殖指数，并且具有最少的细胞处于细胞周期的G2/M（有丝分裂）期的细胞数。此外，NB 10也是最敏感的肿瘤坏死因子相关的凋亡诱导配体（TRAIL）或依托泊苷诱导的细胞death.Conclusions：在原发性NB肿瘤，生存素表达与肿瘤的高风险和预后不良，而促凋亡受体的表达更丰富的肿瘤预后良好。在这个小系列中，生存素表达似乎比N-myc扩增更能预测疾病的复发。在细胞系中，生存素的表达是细胞周期依赖性的，并且其表达与对药物或免疫介导的细胞死亡的更大抗性相关。Survivin的表达可能成为NB的一个有用的预后指标，并可能成为治疗该肿瘤的潜在靶点。少

Background/Purpose : Apoptotic factors inducing or preventing cell death may intrinsically govern the behavior of some tumors. Survivin is a recently described member of the inhibitor of apoptosis protein (IAP) family, that is expressed in a cell cycle-dependent manner and is found in tumors of unfavorable histology. This study examines the presence of several apoptotic factors, including survivin, in neuroblastoma (NB) tumors. Clues to surviving function in NB are provided by examining its association with behavior and cell dynamics in tumors and cell lines.Methods : Expression of a panel of apoptosis factors were quantified in 15 NB and related tumors before chemotherapy and in 3 NB cell lines (NB7, N810, and NB16). Survivin and other apoptotic factors, as well N-myc amplification in primary tumors was correlated with recurrent disease and outcome. Proliferation rate, apoptosis assays, cell cycle analysis, and drug- or immune-mediated cell death were assessed in cell lines and evalua … More ted in the context of differential survivin and apoptosis gene expression.Results : All 7 tumors that went on to recur expressed survivin, whereas expression was absent in all 8 tumors that went into remission. N-myc was amplified in 4 (57.1%) of the 7 recurrent tumors. Of the 8 tumors that were cured. Fas was expressed in 3 (38%), TRAIL-R1 in 6 (75%) and tumor necrosis factor (TNF)-R1 in 8 (100%), whereas these pro-apoptotic receptors were present in only 1 (14%), 1 (14%), and 4 (57%) of the 7 tumors that went on to recur, respectively. Of the 3 cell lines, NB10 expressed the least survivin, displayed the lowest proliferation index, and had the fewest number of cells in the G2/M (mitotic) phase of the cell cycle. Furthermore, NB10 also was most sensitive to TNF-related apoptosis-inducing ligand (TRAIL) or etoposide-induced cell death.Conclusions : In primary NB tumors, survivin expression was associated with tumors of high risk and unfavorable prognosis, whereas pro-apoptotic receptor expression was more abundant in tumors of favorable prognosis. In this small series, survivin expression appeared to be more predictive of recurrent disease than N-myc amplification. In cell lines, survivin expression was cell cycle dependent, and its expression was associated with greater resistance to drug- or immune-mediated cell death. Survivin expression may become a useful prognostic marker in NB and could be a potential target for the treatment of this tumor. Less