期刊
CLINICAL CANCER RESEARCH
卷 19, 期 9, 页码 2319-2330出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-12-3151
关键词
-
类别
资金
- Ministerio de Ciencia e Innovacion [SAF2008-03871]
- Fondo de Investigaciones Sanitarias [FIS 08/0856, RTICC RD06/0020/0107]
- Asociacion Espanola Contra el Cancer
- Comunidad Autonoma de Madrid, Spain
- Miguel Servet contract from the Fondo de Investigaciones Sanitarias [CP11/00018]
Purpose: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated NF-kappa B activity has been associated with several lymphoproliferative diseases, but its importance in T-cell lymphomagenesis is poorly understood. We investigated the function of the NF-kappa B-inducing kinase (NIK), in this pathway and its role as a potential molecular target in T-cell lymphomas. Experimental Design: We used immunohistochemistry to analyze the expression of different NF-kappa B members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T-cell lymphoma cell lines and observed its effect on downstream targets and cell viability. Results: We showed that the NF-kappa B pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples, and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than inhibitor of kappa B kinase (IKK) knockdown. NIK silencing induced a blockage of both classical and alternative NF-kappa B activation and reduced expression of several prosurvival and antiapoptotic factors. Conclusions: The results of the present study indicate that NIK could be a promising therapeutic target in these aggressive malignancies. (c) 2013 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据