C/EBPα和C/EBPβ抑制PHLPP的表达影响细胞增殖  

Effect of the PHLPP Expression Inhibited by C/EBPα and C/EBPβ on the Cell Proliferation

作　　者：王亚棋 黎隽 刘立科 刘东鸣 韩溟 李剑利[2] Wang Yaqi;Li Jun;Liu Like;Liu Dongming;Han Ming;Li Jianli(Shaanxi Medical Devices Quality Supervision and Inspection Institute,Xi'an 712046,China;College of Chemistry & Materials Sciences,Northwest University,Xi'an 710127,China)

机构地区：[1]陕西省医疗器械质量监督检验院,西安712046 [2]西北大学化学与材料科学学院,西安710127

出　　处：《成都医学院学报》2018年第6期651-657,661,共8页Journal of Chengdu Medical College

基　　金：国家自然科学基金项目(No:30970653)

摘　　要：目的分析影响抑癌基因磷酸酶PHLPP表达的因素,进一步研究肿瘤发生、发展的机制。方法分析比对多种种属的PHLPP基因序列,根据其启动子中均有碱性亮氨酸拉链(basic leucine zipper,bZIP)转录因子C/EBPα、C/EBPβ的结合位点,也有SP1的结合位点这一特点,通过双荧光素酶报告法和染色质免疫共沉淀(chromatin immunoprecipitation assay,ChIP),过表达或抑制C/EBPα、C/EBPβ的表达,再通过PCR、RT-PCR、Western blot、细胞生长实验和肿瘤组织切片免疫组化进行分析。结果 C/EBPα和C/EBPβ与PHLPP的启动子相结合并抑制其表达,与PHLPP的表达呈负相关,SP1不影响PHLPP的表达。结论 C/EBPα和C/EBPβ通过作用于PHLPP影响细胞增殖。Objective To explore the mechanism of tumor occurrence and development by studying the influencing factors of the expression of the tumor suppressor gene phosphatase pleckstrin homology domain leucine-rich repeat protein phosphatase(PHLPP).Methods On the basis of the characteristic that the PHLPP promoter sequence contained the binding sites of the basic leucine zipper(bZIP)transcriptional factors C/EBPαand C/EBPβand the binding site of SP1,the dual luciferase reporter gene assay and chromatin immunoprecipitation assay were used to arouse the overexpression or inhibited expression of C/EBPαand C/EBPβ,and the methods of PCR,RT-PCR,Western blot,cell growth experiment,and immunohistochemical analysis assay of tumor tissue sections were used to compare the PHLPP gene sequences of various genera.Results C/EBPαand C/EBPβbound with the promoter of PHLPP and inhibted its expression.They were negatively correlated with the expression of PHLPP,which was not affected by SP1.Conclusion C/EBPαand C/EBPβcould affect the proliferation of tumor cells by inhibiting the PHLPP expression.

关 键 词：转录因子c/ebp 磷酸酶PHLPP 细胞增殖 

分 类 号：R730.2[医药卫生—肿瘤]