RRC ID 38173
Author Takayama Y, Kokuryo T, Yokoyama Y, Ito S, Nagino M, Hamaguchi M, Senga T.
Title Silencing of Tousled-like kinase 1 sensitizes cholangiocarcinoma cells to cisplatin-induced apoptosis.
Journal Cancer Lett
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.
Volume 296(1)
Pages 27-34
Published 2010-10-1
DOI 10.1016/j.canlet.2010.03.011
PII S0304-3835(10)00148-5
PMID 20381954
MeSH Antimetabolites, Antineoplastic / pharmacology Apoptosis / drug effects* Bile Duct Neoplasms / genetics* Bile Duct Neoplasms / pathology Bile Ducts, Intrahepatic Cell Line, Tumor Cholangiocarcinoma / genetics* Cholangiocarcinoma / pathology* Cisplatin / pharmacology* DNA Repair / genetics DNA Replication / genetics Deoxycytidine / analogs & derivatives Deoxycytidine / pharmacology Fibroblasts / cytology Fibroblasts / physiology Foreskin / cytology Foreskin / physiology Gemcitabine Gene Knockdown Techniques Gene Silencing* Humans In Situ Nick-End Labeling Male Protein Serine-Threonine Kinases / drug effects Protein Serine-Threonine Kinases / genetics* RNA, Small Interfering / genetics Reverse Transcriptase Polymerase Chain Reaction Transfection
IF 7.36
Times Cited 14
WOS Category ONCOLOGY
Resource
Human and Animal Cells