Overexpression of survivin initiates hematologic malignancies in vivo.

Overexpression of survivin initiates hematologic malignancies in vivo.
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DOI:
10.1038/leu.2010.198
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发表时间:
2010-11
期刊:
影响因子:
11.4
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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Survivin是IAP家族成员,作为染色体乘客复合体的重要组成部分,在细胞增殖中发挥重要作用。存活素在胚胎和增殖的成体组织中高度表达,但在大多数分化的细胞中不表达。然而,在肿瘤发生过程中,生存素表达显著上调。尽管许多研究表明,生存素是癌细胞所必需的,但生存素在肿瘤发生中的作用程度尚不清楚。在这里,我们表明,在造血细胞中过表达生存素的转基因小鼠发生血液肿瘤的风险增加。在研究生存素如何可能有助于肿瘤发生的过程中,我们观察到,经过基因工程改造过表达生存素的造血细胞对凋亡不太敏感。我们的结论是,生存素可能会促进肿瘤发生的细胞,获得额外的遗传病变的生存优势。
Survivin is an IAP family member that plays an essential role in cellular proliferation as an essential component of the chromosome passenger complex. Survivin is highly expressed in embryos and in proliferating adult tissues, but it is not expressed in most differentiated cells. During tumorigenesis, however, survivin expression is dramatically upregulated. Although many studies have shown that survivin is required for cancer cells, the extent to which survivin contributes to the initiation of tumors is unknown. Here we show that transgenic mice that overexpress survivin in hematopoietic cells are at an increased risk of hematologic tumors. In examining how survivin might contribute to tumorigenesis, we observed that hematopoietic cells engineered to overexpress survivin are less susceptible to apoptosis. We conclude that survivin may promote tumorigenesis by imparting a survival advantage to cells that acquire additional genetic lesions.
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