TY - JOUR
T1 - RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells
AU - Hata, Tatsuo
AU - Furukawa, Toru
AU - Sunamura, Makoto
AU - Egawa, Shinichi
AU - Motoi, Fuyuhiko
AU - Ohmura, Noriyuki
AU - Marumoto, Tomotoshi
AU - Saya, Hideyuki
AU - Horii, Akira
PY - 2005/4/1
Y1 - 2005/4/1
N2 - AURKA/STK15/BTAK, the gene encoding Aurora A kinase that is involved in the regulation of centrosomes and segregation of chromosomes, is frequently amplified and overexpressed in various kinds of human cancers, including pancreatic cancer. To address its possibility as a therapeutic target for pancreatic cancer, we employed the RNA interference technique to knockdown AURKA expression and analyzed its phenotypes. We found that the specific knockdown of AURKA in cultured pancreatic cancer cells strongly suppressed in vitro cell growth and in vivo tumorigenicity. The knockdown induced the accumulation of cells in the G2-M phase and eventual apoptosis. Furthermore, we observed a synergistic enhancement of the cytotoxicity of taxanes, a group of chemotherapeutic agents impairing G2-M transition, by the RNA interference-mediated knockdown of AURKA. These results indicate that inhibition of AURKA expression can result in potent antitumor activity and chemosensitizing activity to taxanes in human pancreatic cancer.
AB - AURKA/STK15/BTAK, the gene encoding Aurora A kinase that is involved in the regulation of centrosomes and segregation of chromosomes, is frequently amplified and overexpressed in various kinds of human cancers, including pancreatic cancer. To address its possibility as a therapeutic target for pancreatic cancer, we employed the RNA interference technique to knockdown AURKA expression and analyzed its phenotypes. We found that the specific knockdown of AURKA in cultured pancreatic cancer cells strongly suppressed in vitro cell growth and in vivo tumorigenicity. The knockdown induced the accumulation of cells in the G2-M phase and eventual apoptosis. Furthermore, we observed a synergistic enhancement of the cytotoxicity of taxanes, a group of chemotherapeutic agents impairing G2-M transition, by the RNA interference-mediated knockdown of AURKA. These results indicate that inhibition of AURKA expression can result in potent antitumor activity and chemosensitizing activity to taxanes in human pancreatic cancer.
UR - http://www.scopus.com/inward/record.url?scp=16844366286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=16844366286&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-04-3981
DO - 10.1158/0008-5472.CAN-04-3981
M3 - Article
C2 - 15805292
AN - SCOPUS:16844366286
SN - 0008-5472
VL - 65
SP - 2899
EP - 2905
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -