Silencing of Tousled-like kinase 1 sensitizes cholangiocarcinoma cells to cisplatin-induced apoptosis.
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.
Takayama
Yuichi
Y
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Japan.
Kokuryo
Toshio
T
Yokoyama
Yukihiro
Y
Ito
Satoko
S
Nagino
Masato
M
Hamaguchi
Michinari
M
Senga
Takeshi
T
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D052816:Foreskin / Q000166:cytology / Q000502:physiology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D017346:Protein Serine-Threonine Kinases; C425323:TLK1 protein, human; D002945:Cisplatin; D000093542:Gemcitabine