Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer.
Previous studies have demonstrated amplification of the centrosome serine/threonine kinase BTAK/Aurora-A in 10-25% of ovarian cancers. However, alterations of BTAK/Aurora-A at kinase and protein levels and its role in ovarian cancer progression have not been well documented. In this study, we examined the kinase activity and protein levels of BTAK/Aurora-A in 92 patients with primary ovarian tumors. In vitro kinase analyses revealed elevated BTAK/Aurora-A kinase activity in 44 cases (48%). Increased BTAK/Aurora-A protein levels were detected in 52 (57%) specimens. High protein levels of BTAK/Aurora-A correlated well with elevated kinase activity. Activation and overexpression of BTAK/Aurora-A were more frequently detected in early stage/low-grade ovarian tumors, although there was no statistic significance at the kinase level between early stage/low-grade and late stage/high-grade tumors. Moreover, BTAK/Aurora-A was preferentially expressed in noninvasive tumors, as revealed by immunohistochemical staining, suggesting that alterations of BTAK/Aurora-A could be an early event in human ovarian oncogenesis. To our knowledge, this is the first demonstration of recurrent activation and overexpression of BTAK/Aurora-A in human ovarian cancer, which may play a critical role in development of this malignancy.
Gritsko
Tatiana M
TM
Department of Pathology and Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
Coppola
Domenico
D
Paciga
June E
JE
Yang
Lin
L
Sun
Mei
M
Shelley
Sue A
SA
Fiorica
James V
JV
Nicosia
Santo V
SV
Cheng
Jin Q
JQ
D064096:Aurora Kinase A; D064127:Aurora Kinases; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases