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.