Regulation of CD137 expression through K-Ras signaling in pancreatic cancer cells

作     者：Christophe Glorieux Peng Huang 

作者机构：Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China 

出 版 物：《Cancer Communications》 (癌症通讯（英文）)

年 卷 期：2019年第39卷第1期

页      面：379-389页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported in part by a Grant from the National Natural Science Foundation of China(No.81430060) 

主　　题：CD137 K-Ras IL-1α(interleukin-1 alpha) MAPK(mitogen-activated protein kinases) NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells) Pancreatic cancer Oxidative stress Soluble CD137 

摘      要：Background:The interaction between CD137 and its ligand(CD137L)plays a major role in the regulation of immune functions and affects cancer ***137 is a cell surface protein mainly located on activated T cells,and its regulation and functions in immune cells are well ***,the expression of CD137 and its regulation in cancer cells remain poorly *** main purposes of this study were to examine the expression of CD137 in pancreatic cancer cells and to investigate its underlying ***:Cells containing inducible K-RasG12V expression vector or with different K-Ras mutational statuses were used as in vitro models to examine the regulation of CD137 expression by *** molecular assays were employed to explore the regulatory *** specimens from 15 pancreatic cancer patients and serum samples from 10 patients and 10 healthy donors were used to test if the expression of CD137 could be validated in clinical ***:We found that the CD137 protein was expressed on the cell surface in pancreatic cancer tissues and cancer cell ***-linked immunosorbent assay revealed no difference in the levels of secreted CD137 in the sera of patients and healthy *** using the K-Ras inducible cell system,we further showed that oncogenic K-Ras up-regulated CD137 through the activation of MAPK(mitogen-activated protein kinases)and NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells)pathways,as evidenced by significantly reduced CD137 mRNA expression led by genetic silencing of MAPK1 and p65,the key proteins involved in the respective ***-more,we also found that the NF-κB pathway was mainly stimulated by the K-Ras-induced secretion of interleukin-1α(IL-1α)which promoted the transcription of the CD137 gene in pancreatic cancer cell *** of the TCGA(the cancer genome atlas)database also revealed a significant correlation between IL-1αand CD137 expression(r=0.274)in tumor s