Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death.
Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death.
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DOI：
10.1002/ijc.23548
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发表时间：
2008-08-01
影响因子：
6.4
通讯作者：
Wang, Fen
中科院分区：
文献类型：
--
作者：
Lan, Yongsheng;Zhang, Yongyou;Wang, Jianghua;Lin, Chunhong;Ittmann, Michael M.;Wang, Fen
哺乳动物Cks家族由两个高度保守的小蛋白Cks 1和Cks 2组成。cks 1已经显示通过触发p27 kip 1的降解来促进细胞周期进程。尽管Cks 2在减数分裂期间的第一个中期/后期转变中是必需的，但它在哺乳动物体细胞中的功能尚不清楚。越来越多的证据表明，Cks 1和Cks 2的高表达常出现在多种肿瘤中，并且与患者的低生存率相关。在这里，我们证明了Cks 1和Cks 2的表达在人类和动物模型的前列腺肿瘤以及前列腺癌细胞系中升高。Cks 1和Cks 2在良性前列腺肿瘤上皮细胞中的强制表达促进细胞群体生长。在恶性前列腺肿瘤细胞中，敲低Cks 1表达抑制增殖、锚定非依赖性生长和迁移活动，而敲低Cks 2表达诱导细胞程序性死亡并抑制致瘤性。总的来说，这些数据表明，Cks 1的表达升高有助于前列腺肿瘤细胞的致瘤性，通过促进细胞生长和Cks 2的表达升高保护细胞免于凋亡。因此，这一发现表明了一种基于抑制Cks 1和Cks 2活性的前列腺癌新的治疗策略。
The mammalian Cks family consists of two well-conserved small proteins, Cks1 and Cks2. Cks1 has been shown to promote cell cycle progression by triggering degradation of p27kip1. The function of Cks2 in somatic mammalian cells is not well understood although it is required for the first metaphase/anaphase transition during the meiosis. Emerging evidence shows that elevated expression of Cks1 and Cks2 is often found in a variety of tumors, and is correlated with poor survival rate of the patients. Here we demonstrated that expression of Cks1 and Cks2 were elevated in prostate tumors of human and animal models, as well as prostatic cancer cell lines. Forced expression of Cks1 and Cks2 in benign prostate tumor epithelial cells promoted cell population growth. Knockdown of Cks1 expression in malignant prostate tumor cells inhibited proliferation, anchorage-independent growth, and migration activities, whereas knockdown of Cks2 expression induced programmed cell death and inhibited the tumorigenicity. Collectively, the data suggest that elevated expression of Cks1 contributes to the tumorigenicity of prostate tumor cells by promoting cell growth and elevated expression of Cks2 protects the cells from apoptosis. Thus, the finding suggests a novel therapeutic strategy for prostatic cancer based on inhibiting Cks1 and Cks2 activity.
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影响因子：
4.6
作者：
Lin, Yongshun;Liu, Guoqin;Wang, Fen
通讯作者：
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影响因子：
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作者：
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