Deregulation of IKBKE Is Associated with Tumor Progression, Poor Prognosis, and Cisplatin Resistance in Ovarian Cancer
Deregulation of IKBKE Is Associated with Tumor Progression, Poor Prognosis, and Cisplatin Resistance in Ovarian Cancer
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DOI：
10.2353/ajpath.2009.080767
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发表时间：
2009-07-01
影响因子：
6
通讯作者：
Cheng, Jin Q.
中科院分区：
文献类型：
--
作者：
Guo, Jian-Ping;Shu, Shao-Kun;Cheng, Jin Q.
I-kappa-B激酶e(IKBKE；ikk epsilon)是近年来发现的一种乳腺癌癌基因，其改变似乎是乳腺癌发生发展的早期事件。在这项研究中，我们证明了ikk epsilon在人卵巢癌细胞系和原发肿瘤中经常过表达和激活。在接受检查的96例卵巢癌标本中，63例显示IKK epsilon水平升高。此外，ikk epsilon的改变与晚期和高级别肿瘤相关，这表明ikk epsilon在卵巢肿瘤的进展中起作用，而不是在肿瘤的发生中。IKK epsilon水平升高的患者的总体存活率显著低于肿瘤表达正常的患者。此外，早期和晚期的肿瘤都过度表达。与那些没有IKK epsilon水平升高的患者相比，ikk epsilon的预后较差。值得注意的是，在表达高水平内源性IKK epsilon的A2780CP和C13细胞中，过表达ikk epsilon的细胞对顺铂具有耐药性，而敲除ikk epsilon的细胞克服了对顺铂的耐药性。因此，这些数据首次表明，IKK epsilon的去调控在人类卵巢癌中是一个高度复发的事件，并可能在肿瘤进展和顺铂耐药中发挥关键作用。IKK epsilon也可作为判断预后的标志物和潜在的治疗靶点。(Am J Pathol 2009175：324333；DOI：10.2353/ajpath.2009.080767)
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)