Abstract
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 gammaH2AX 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.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Apoptosis / drug effects*
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Bile Duct Neoplasms / genetics*
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Bile Duct Neoplasms / pathology
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Bile Ducts, Intrahepatic
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Cell Line, Tumor
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Cholangiocarcinoma / genetics*
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Cholangiocarcinoma / pathology*
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Cisplatin / pharmacology*
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DNA Repair / genetics
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DNA Replication / genetics
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Fibroblasts / cytology
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Fibroblasts / physiology
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Foreskin / cytology
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Foreskin / physiology
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Gemcitabine
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Gene Knockdown Techniques
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Gene Silencing*
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Humans
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In Situ Nick-End Labeling
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Male
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Protein Serine-Threonine Kinases / drug effects
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Protein Serine-Threonine Kinases / genetics*
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RNA, Small Interfering / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
Substances
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Antimetabolites, Antineoplastic
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RNA, Small Interfering
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Deoxycytidine
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Protein Serine-Threonine Kinases
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TLK1 protein, human
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Cisplatin
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Gemcitabine