title: Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Gritsko
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: June E
authors.initials: JE
authors.lastname: Paciga
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Sue A
authors.initials: SA
authors.lastname: Shelley
authors.forename: James V
authors.initials: JV
authors.lastname: Fiorica
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
mesh_terms: 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
chemical_list: 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