Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma.
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.
Kokuryo
Toshio
T
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Senga
Takeshi
T
Yokoyama
Yukihiro
Y
Nagino
Masato
M
Nimura
Yuji
Y
Hamaguchi
Michinari
M
D000818:Animals; D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology* / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000072379:NIMA-Related Kinases; D010534:Peritoneal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
D018076:DNA, Complementary; D034741:RNA, Small Interfering; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases