RNA interference against Hec1 inhibits tumor growth in vivo
RNA interference against Hec1 inhibits tumor growth in vivo
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DOI：
10.1038/sj.gt.3302595
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发表时间：
2006-01-01
期刊：
影响因子：
5.1
通讯作者：
Izquierdo, M
中科院分区：
文献类型：
--
作者：
Gurzov, EN;Izquierdo, M
Hec 1（在癌症中高度表达）通过与检查点蛋白的子集相互作用在染色体分离中起重要作用，所述检查点蛋白调查正确的染色体对齐和双极纺锤体附着。为了破坏肿瘤细胞系的有丝分裂进程，我们使用了抑制Hec 1合成的逆转录病毒和腺病毒载体。载体表达的短发夹RNA（shRNAs）在人宫颈腺癌（HeLa）和胶质母细胞瘤（U-373-MG）细胞系中引起非常有效的靶蛋白耗尽、细胞停滞和相当大的有丝分裂灾难诱导。此外，与对照组相比，用Hec 1-shRNA逆转录病毒或腺病毒治疗时，在裸鼠胁腹中诱导的腺癌显示出显著的尺寸减小。这些结果表明，Hec 1的缺失可以用作阻断分裂细胞的新策略，从而对抗癌症。
Hec1 ( highly expressed in cancer) plays an important role in chromosome segregation by interacting with a subset of checkpoint proteins that survey proper chromosome alignment and bipolar spindle attachment. In order to disrupt mitotic progression of tumor cell lines, we have used retrovirus and adenovirus vectors that inhibit Hec1 synthesis. Vector-expressed short hairpin RNAs (shRNAs) caused very efficient depletion of the target protein, cellular arrest and considerable mitotic catastrophe induction 96 h post infection in human cervix-adenocarcinoma (HeLa) and glioblastoma (U-373-MG) cell lines. Furthermore, adenocarcinomas induced in the flanks of nude mice show significant reduction in size compared with control when treated with either Hec1-shRNA retroviruses or adenoviruses. These results indicate that depletion of Hec1 could be used as a new strategy to block the dividing cell, and therefore against cancer.