Silencing of Tousled-like kinase 1 sensitizes cholangiocarcinoma cells to cisplatin-induced apoptosis
Silencing of Tousled-like kinase 1 sensitizes cholangiocarcinoma cells to cisplatin-induced apoptosis
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DOI：
10.1016/j.canlet.2010.03.011
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发表时间：
2010-10-01
期刊：
影响因子：
9.7
通讯作者：
Senga, Takeshi
中科院分区：
文献类型：
--
作者：
Takayama, Yuichi;Kokuryo, Toshio;Senga, Takeshi
胆管癌是一种特别具有破坏性的癌症，治疗选择有限。Tousled-like kinase 1（TLK 1）是一种丝氨酸/苏氨酸蛋白激酶，调节DNA复制和DNA修复途径。在这里，我们表明，TLK 1是丰富的表达在胆管癌以及胆管癌细胞系。虽然TLK 1的siRNA敲低不影响胆管癌细胞的生存能力，但它使胆管癌细胞对顺铂诱导的凋亡敏感。γ H2 AX病灶的免疫荧光分析表明，沉默TLK 1增强顺铂治疗诱导的DNA损伤。我们的研究结果表明，TLK 1在顺铂诱导的DNA损伤修复中起着关键作用。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Cholangiocarcinoma is a particularly devastating carcinoma with limited treatment options. Tousled-like kinase 1 (TLK1) is a serine/threonine protein kinase that regulates DNA replication and DNA repair pathways. Here, we show that TLK1 is abundantly expressed in cholangiocarcinoma as well as in cell lines derived from cholangiocarcinoma. Although siRNA knockdown of TLK1 did not affect the viability of cholangiocarcinoma cells, it sensitized cholangiocarcinoma cells to cisplatin-induced apoptosis. Immunofluorescence analysis of gamma H2AX foci showed that silencing of TLK1 enhanced DNA damage induced by cisplatin treatment. Our results suggest that TLK1 plays a pivotal role for the repair of cisplatin-induced DNA damage. (C) 2010 Elsevier Ireland Ltd. All rights reserved.