Keap1在肾细胞癌中的表达及其作用

Expression and role of Keap1 in renal cell carcinoma

目的探讨Kelch样ECH相关蛋白-1(Keap1)在肾癌中的表达及其在肾癌发生发展中的作用。方法采用Q-PCR技术检测32例肾癌患者的肿瘤组织和肾癌旁组织中Keap1、核因子E2相关因子2(NFE2L2)的表达;免疫组织化学染色法检测上述肾癌患者肿瘤组织和肾癌旁组织中Keap1、NFE2L2的表达;CCK-8法检测和克隆形成法检测过表达Keap1后对肾癌细胞系ACHN增殖活性以及克隆形成能力的影响。结果实时荧光定量PCR(Q-PCR)结果显示,75.00%患者Keap1 mRNA的表达癌旁组织高于肿瘤组织(P=0.000),62.50%患者NFE2L2mRNA的表达肿瘤组织高于癌旁组织(P=0.046)。免疫组化结果显示32例肾癌患者中,Keap1蛋白在癌旁组织(87.50%)的表达高于肿瘤组织(25.00%)(P=0.000),NFE2L2蛋白在肿瘤组织(81.25%)的表达高于癌旁组织(46.88%)(P=0.004)。高表达Keap1后,NFE2L2的表达降低,肾癌细胞系ACHN的增殖能力和克隆形成能力降低。结论 Keap1/NFE2L2通路在肾癌的发生和发展中可能发挥重要作用,Keap1的表达对肾癌可能起到抑制作用。

Objective To investigate the expression of Keap1 and evaluate its role in renal carcinoma.Methods The total RNA of tumor tissues and adjacent tissues were isolated from 32 cases of renal carcinoma treated during M ay 2014 to April 2015 by TRIzol.The expressions of Keap1 and NFE2L2 were detected by Q-PCR technology and immunohistochemical staining.The changes of proliferation and colony forming ability of ACHN after overexpressed Keap1 were detected by CCK-8 cell proliferation and clone formation assay.Results Q-PCR results showed that the expression of Keap1 mRNA in adjacent tissues in 75% patients was higher than that in tumor tissues（P=0.000）,the expression of NFE2L2 mRNA in tumor tissues in 62% patients was higher than that in adjacent tissues（P=0.046）.The immunohistochemical results showed that the expression of Keap1 protein in adjacent tissues（87.50%） was higher than that in tumor tissues（25.00%）（P=0.000）,and the expression of NFE2L2 protein in tumor tissues（81.25%） was higher than that in adjacent tissues（46.88%）（P=0.004）.Overexpression of Keap1 decreased proliferation and colony forming ability of renal cell carcinoma cell line ACHN.Conclusion The abnormal expression of Keap1 in tumor tissues indicates that the Keap1-NFE2L2 pathway may play an important role in renal carcinoma.Keap1 has a probable inhibiting effect on the progression of renal carcinoma.