抑癌基因PRDM1在结外NK/T细胞淋巴瘤-鼻型中的表达及其与PI3K/AKT通路活化的关系
PRDM1 expression and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type
目的 探讨抑癌基因PRDM1在结外NK/T细胞淋巴瘤-鼻型(EN-NK/T-NT)中的表达及其与PI3K/AKT通路活化的关系.方法 以10例EN-NK/T-NT患者病理组织标本和PRDM1阳性细胞系YT细胞、PRDM1缺失细胞系NKL、NK92细胞为研究对象,采用免疫细胞化学和Western blot法检测PRDM1、p-AKT的表达,采用NanoString基因表达谱技术检测PI3K/AKT通路在正常鼻黏膜、PRDM1阴性和阳性EN-NK/T-NT组织中的激活情况,采用MTS法检测YT、NKL和NK92细胞增殖活性,采用流式细胞术检测细胞周期和细胞凋亡.结果 ①NanoString基因表达谱分析结果显示PRDM1阳性组PI3K/AKT信号通路IL-7、BRCA1、ITGA8、IL2RB、FASLG、CDK2、COL27A1、CSF3R、KITLG、IL-6的表达明显高于对照组,差异均有统计学意义(P值均<0.05).②免疫细胞化学和Western blot法检测结果显示p-AKT在YT细胞系中高表达,而在NK92和NKL细胞中低表达或不表达.③Western blot法检测结果显示,PI3K/AKT通路抑制剂LY294002作用24h后YT细胞PRDM1和PTEN的表达水平升高,且呈剂量依赖性.④LY294002(20 μmol/L)作用48 h后,与对照组比较,YT细胞增殖率较对照组明显降低(100.00%对58.18%,t=-12.770,P=0.006),G1期细胞比例明显增高(30.05%对76.93%,t=11.570,P<0.001),差异均有统计学意义;但NKL细胞与对照组比较细胞增殖和细胞周期的差异均无统计学意义(P值均> 0.05).结论 EN-NK/T-NT中PI3K/AKT通路活化与PRDM1阳性表达相关,抑制PI3K/AKT通路有望成为PRDM1阳性EN-NK/T-NT的治疗手段.
更多Objective To investigate the expression of PRDM1 and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type.Methods Immunocytoehemistry and Western blot were used to detect the expression of PRDM 1 and p-AKT in 10 EN-NK/T-NT tissue or 3 cell lines (PRDM1-positive YT cell line,PRDM1-negative NKL and NK92 cell lines).Nanostring gene expression profiling technique was used to detect the activation of the PI3K/AKT pathway in normal nasal mucosa,PRDM1-negative and positive EN-NK/T-NT tissue.MTS was used to detect cell proliferation,and flow cytometry was used to detect cell cycle and apoptosis.Results Nanostring gene expression profiling revealed that genes associated with PI3K/AKT signaling pathway (eg,IL-7,BRCA1,ITGA8,IL2RB,FASLG,CDK2,COL27A1,CSF3R,KITLG and IL-6) were highly expressed in EN-NK/T-NT cases (P <0.05).Also,we found that p-AKT was highly expressed in YT cell line,but lower or not expressed in NK92 and NKL cells.In addition,LY294002,a PI3K/AKT pathway inhibitor,increased PRDM1 and PTEN expression in a dose dependent manner in YT cells.More importantly,YT cell were treated with 20 μmol/LLY294002 48 h,the proliferation rate was significantly decreasing (58.18% vs 100.00%,t=12.770,P=0.006),and the proportion of cells in G1 phase was significantly increased (30.05% vs 76.93%,t =11.570,P < 0.001).However,there was no significant difference in cell proliferation and cell cycle between NKL cells and control group (P> 0.05).Conclusion The activation of PI3K/AKT pathway is positive associated with the expression of PRDM 1 in EN-NK/T-NT,and inhibition of PI3K/AKT pathway may have significant therapeutic potential for PRDM 1-positive EN-NK/T-NT.
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