Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma
Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma
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DOI：
10.1158/0008-5472.can-07-1489
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发表时间：
2007-10-15
期刊：
影响因子：
11.2
通讯作者：
Hamaguchi, Michinari
中科院分区：
文献类型：
--
作者：
Kokuryo, Toshio;Senga, Takeshi;Hamaguchi, Michinari
我们研究了丝氨酸/苏氨酸激酶家族Nek的成员Nek 2在胆管癌细胞致瘤性生长中的作用。与正常成纤维细胞相比，Nek 2的表达在胆管癌中以肿瘤特异性方式升高。外源性Nek 2的表达并不干扰胆管癌细胞的生长，而用siRNA抑制Nek 2的表达导致细胞增殖抑制和诱导细胞死亡。在异种移植物-裸鼠模型中，s.c.在肿瘤结节周围注射Nek 2 siRNA导致肿瘤尺寸与对照siRNA注射相比减小。在腹膜播散模型中，Nek 2 siRNA处理的小鼠与对照siRNA处理的小鼠相比显示出统计学上更长的存活期。总之，我们的数据表明Nek 2在胆管癌的致瘤性生长中起关键作用。
We investigated the role of Nek2, a member of the serine/ threonine kinase family, Nek, in the tumorigenic growth of cholangiocarcinoma cells. Expression of Nek2 is elevated in cholangiocarcinoma in a tumor-specific manner as compared with that of normal fibroblast cells. Expression of exogenous Nek2 did not perturb the growth of cholangiocarcinoma cells, whereas suppression of the Nek2 expression with siRNA resulted in the inhibition of cell proliferation and induced cell death. In xenograft-nude mouse model, s.c. injection of Nek2 siRNA around the tumor nodules resulted in reduction of tumor size as compared with those of control siRNA injection. In peritoneal dissemination model, Nek2 siRNA-treated mice showed statistically longer survival periods in comparison with those of the control siRNA-treated mice. Taken together, our data indicate a pivotal role of Nek2 in tumorigenic growth of cholangiocarcinoma.