组蛋白去乙酰化酶抑制剂调控p21WAF1/CIP1启动子乙酰化水平影响乳腺癌MCF-7细胞周期

摘要

目的 研究组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACI)调控p21WAF1/CIP1启动子乙酰化水平,调节乳腺癌MCF-7细胞周期的分子机制.方法 采用实时定量PCR、Western blot和DNA-ChIP方法测定SAHA对乳腺癌MCF-7细胞周期调控系统的影响;应用染色质免疫沉淀(chromatin immunoprecipitation, ChIP)技术探究SAHA调控p21WAF1/CIP1启动子乙酰化水平的情况.结果 SAHA明显影响乳腺癌细胞周期相关调控因子的表达;在针对p21WAF1/CIP1基因功能的筛查中发现,SAHA可明显诱导p21WAF1/CIP1 mRNA和蛋白的表达,并且可调节p21WAF1/CIP1启动子乙酰化水平.结论 SAHA通过影响p21WAF1/CIP1启动子乙酰化程度调节乳腺癌MCF-7细胞周期的进程.%Aim To study the regulation mechanisms of deacetylase inhibitor SAHA in p21WAF1/CIP1 promoter acetylation in breast cancer MCF-7 cells.Methods We used quantitative real-time PCR, Western blot and DNA-ChIP to determine the effects on the regulation of cell cycle with SAHA treatment in MCF-7 cells.By DNA-ChIP, we assessed the acetylation level of p21WAF1/CIP1 promoter.Results SAHA significantly affected the expression of cell cycle-related factors, and induced the mRNA and protein expression of p21WAF1/CIP1.SAHA could adjust the acetylation level of p21WAF1/CIP1 promoter.Conclusion SAHA regulates the cell cycle progression by adjusting the acetylation level of p21WAF1/CIP1 promoter in MCF-7 cells.