Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Cancer Cell. 2013 Jan 14;23(1):48-62. doi: 10.1016/j.ccr.2012.12.001.
Using sequential gene expression profiling (GEP) samples, we defined a major functional group related to drug resistance that contains chromosomal instability (CIN) genes. One CIN gene in particular, NEK2, was highly correlated with drug resistance, rapid relapse, and poor outcome in multiple cancers. Overexpressing NEK2 in cancer cells resulted in enhanced CIN, cell proliferation and drug resistance, while targeting NEK2 by NEK2 shRNA overcame cancer cell drug resistance and induced apoptosis in vitro and in a xenograft myeloma mouse model. High expression of NEK2 induced drug resistance mainly through activation of the efflux pumps. Thus, NEK2 represents a strong predictor for drug resistance and poor prognosis in cancer and could be an important target for cancer therapy.
利用序贯基因表达谱（GEP）样本，我们定义了一个与耐药性相关的主要功能群，其中包含染色体不稳定性（CIN）基因。特别是 CIN 基因中的一个，NEK2，与多种癌症的耐药性、快速复发和不良预后高度相关。在癌细胞中过表达 NEK2 导致 CIN、细胞增殖和耐药性增强，而通过 NEK2 shRNA 靶向 NEK2 则克服了癌细胞的耐药性，并在体外和骨髓瘤小鼠异种移植模型中诱导了细胞凋亡。NEK2 的高表达主要通过激活外排泵诱导耐药性。因此，NEK2 是癌症耐药性和不良预后的强有力预测因子，可能是癌症治疗的重要靶点。
