Deregulation of IKBKE Is Associated with Tumor Progression, Poor Prognosis, and Cisplatin Resistance in Ovarian Cancer

I-kappa-B kinase e (IKBKE; IKK epsilon) has been recently identified as a breast cancer oncogene, and its alteration appears to be an early event in breast cancer development. in this study, we demonstrated that IKK epsilon is frequently overexpressed and activated in human ovarian cancer cell lines and primary tumors. Of 96 ovarian cancer specimens examined, 63 exhibited elevated levels of IKK epsilon. Furthermore, alterations of IKK epsilon were associated with late-stage and high-grade tumors, suggesting a role of IKK epsilon in ovarian tumor progression rather than in tumor initiation. Overall survival in patients with elevated levels of IKK epsilon was significantly lower than patients whose tumors expressed normal levels of IKK epsilon. Moreover, both early and late-stage tumors that overexpressed. IKK epsilon conferred a poor prognosis, as compared with those that did not possess elevated IKK epsilon levels. Notably, overexpression of IKK epsilon rendered cells resistant to cisplatin, whereas knockdown of IKK epsilon overcame cisplatin resistance in both A2780CP and C13 cells, which express high levels of endogenous IKK epsilon. Therefore, these data demonstrate for the first time that deregulation of IKK epsilon is a highly recurrent event in human ovarian cancer and could play a pivotal role in tumor progression and cisplatin resistance. IKK epsilon could also serve as a prognostic marker and potential therapeutic target for this malignancy. (Am J Pathol 2009,175:324-333; DOI: 10.2353/ajpath.2009.080767)