IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma  

作　　者：Liang Wang Xi-wen Bi Yu-jia Zhu Ying-zhi He Qiu-yu Lai Zhong-jun Xia Qing-qing Cai 

机构地区：[1]Department of Hematology,ZhuJiang Hospital,Southern Medical University,Guangzhou 510280,Guangdong,P.R.China [2]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,Guangdong,P.R.China [3]Department of Medical Oncology,Sun Yat-sen University Cancer Center,Guangzhou 510060,Guang-dong,P.R.China [4]Department of Radiation Oncology,Sun Yat-sen University Cancer Center,Guangzhou 510060,Guangdong,P.R.China [5]Department of Hematologic Oncology,Sun Yat-sen University Cancer Center,Guangzhou 510060,Guangdong,P.R.China

出　　处：《Cancer Communications》2018年第1期667-676,共10页癌症通讯（英文）

基　　金：the National Natural Science Foundation of China(81400159,81873450,81700196,81672686);Pearl River Nova Program of Guangzhou(201710010161);Sister Institution Net-work Fund of the MD Anderson Cancer Center(to Qingqing Cai);the Fundamental Research Funds for the Central Universities(17ykpy77).

摘　　要：Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy.Serum level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and survival.In the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell lines.Methods:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6.Lentiviral vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 cells.The biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were analyzed.Results:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 cells.Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and asparaginase.These effects were reversed by an anti-IL-2Rαantibody.Conclusions:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rαexpression.IL-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.

关 键 词：Natural killer/T-cell lymphoma Latent membrane protein 1 Epstein-Barr virus Interleukin-2 receptor alpha 

分 类 号：R73[医药卫生—肿瘤]