Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias.
Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias.
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发表时间：
2000-05
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通讯作者：
I. Tamm;S. Kornblau;H. Segall;S. Krajewski;K. Welsh;S. Kitada;D. Scudiero;G. Tudor;Y. Qui;A. Monks;M. Andreeff;John Calvin Reed
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作者：
I. Tamm;S. Kornblau;H. Segall;S. Krajewski;K. Welsh;S. Kitada;D. Scudiero;G. Tudor;Y. Qui;A. Monks;M. Andreeff;John Calvin Reed
在美国国家癌症研究所的60种人类肿瘤细胞系中研究了几种凋亡抑制蛋白（IAP）的表达，并在78例未经治疗的急性髓性白血病（AML）患者中评价了其中一种XIAP的表达和预后意义。XIAP和cIAP 1在分析的大多数癌细胞系中表达，其相对水平存在很大差异。与此相反，NAIP mRNA是不可检测的，和cIAP 2被发现在mRNA和蛋白质水平上，只有34（56%）和5（8%）的60个肿瘤细胞系分析，分别。有趣的是，XIAP，cIAP 1和cIAP 2 mRNA水平与肿瘤细胞系中的蛋白水平无关，表明表达的转录后调节。肿瘤细胞系中高水平的XIAP蛋白出乎意料地与对一些抗癌药物的敏感性相关，特别是阿糖胞苷和其他核苷，而较高水平的cIAP 1蛋白水平与对几种抗癌药物的耐药性相关。在AML中探索了XIAP与对阿糖胞苷的体内应答的相关性，与患者结果相关（n = 78）。与XIAP水平较高的患者相比，XIAP蛋白水平较低的患者生存期显著延长（中位数，133 vs 52.5周; P = 0.05），缓解持续时间也有延长的趋势（中位数，87 vs 52.5周; P = 0.13）。总之，这些发现表明IAP在人类癌症和白血病中广泛但差异表达，并表明较高的XIAP蛋白水平可能对AML患者具有不良预后意义。
Expression of several inhibitor of apoptosis proteins (IAPs) was investigated in the National Cancer Institute panel of 60 human tumor cell lines, and the expression and prognostic significance of one of these, XIAP, was evaluated in 78 previously untreated patients with acute myelogenous leukemia (AML). XIAP and cIAP1 were expressed in most cancer lines analyzed, with substantial variability in their relative levels. In contrast, NAIP mRNA was not detectable, and cIAP2 was found at the mRNA and protein levels in only 34 (56%) and 5 (8%) of the 60 tumor cell lines analyzed, respectively. Interestingly, XIAP, cIAP1, and cIAP2 mRNA levels did not correlate with protein levels in the tumor lines, indicating posttranscriptional regulation of expression. High levels of XIAP protein in tumor cell lines were unexpectedly correlated with sensitivity to some anticancer drugs, particularly cytarabine and other nucleosides, whereas higher levels of cIAP1 protein levels were associated with resistance to several anticancer drugs. The relevance of XIAP to in vivo responses to cytarabine was explored in AML, making correlations with patient outcome (n = 78). Patients with lower levels of XIAP protein had significantly longer survival (median, 133 versus 52.5 weeks; P = 0.05) and a tendency toward longer remission duration (median, 87 versus 52.5 weeks; P = 0.13) than those with higher levels of XIAP. Altogether, these findings show that IAPs are widely but differentially expressed in human cancers and leukemias and suggest that higher XIAP protein levels may have adverse prognostic significance for patients with AML.