启动子区甲基化和组蛋白乙酰化对人食管鳞癌细胞SFRP1基因表达的影响  

Effects of histone acetylation and promoter methylation on SFRP1 expression in human esophageal squamous cell carcinoma cells

作　　者：孟莹[1] 朱圣韬[1] 李鹏[1] 张澍田[1] 

机构地区：[1]首都医科大学附属北京友谊医院消化科国家消化系统疾病临床医学研究中心北京市消化疾病中心消化疾病癌前病变北京市重点实验室,北京100050

出　　处：《胃肠病学和肝病学杂志》2015年第5期506-509,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家重点基础研究发展计划(2012CB526600)

摘　　要：目的探讨食管鳞癌(ESCC)细胞株中分泌型卷曲相关蛋白(SFRP)1基因表达与启动子区甲基化和乙酰化的关系。方法采用RT-PCR方法检测SFRP1 mRNA表达,并用甲基化特异性PCR(MSP)方法检测SFRP1基因启动子区甲基化状态,检测5-氮杂脱氧胞苷(DAC)及曲古抑菌素(TSA)对SFRP1基因核酸表达情况的影响。染色质免疫共沉淀方法检测SFRP1基因启动子区域组蛋白乙酰化状态。结果 ESCC细胞株的甲基化率高于正常细胞株。应用DAC及TSA联合处理ESCC细胞株可恢复SFRP1mRNA表达。ESCC细胞株中SFRP1基因启动子区域存在乙酰化组蛋白H3、H4。结论 ESCC细胞株中存在SFRP1基因高甲基化及组蛋白乙酰化。启动子区甲基化和组蛋白乙酰化可能是SFRP1基因表达沉默的主要原因。Objective To investigate the effect of histone acetylation and promoter methylation on the expression of SFRP1 gene in esophageal squamous cell carcinoma （ESCC） cells. Methods Reverse transcriptase-polymerase chain reaction （RT-PCR）, methylation-specific PCR （MSP） and chromatin immunoprecipitation assay were used to detect the mRNA expression, promoter methylation, and histone modification in SFRP1 promoter region in ESCC cell lines. After treated with demethylating agent 5-aza-deoxycytydine （DAC） and histone deacetylase inhibitor Trichostatin A （TSA）, the changes of SFRP1 mRNA expression was detected by RT-PCR. Results The positive rate of SFRP1 promoter methy- lation in ESCC was significantly higher in ESCC cell lines. After treated with DAC and TSA in EC9706 cell line, SFRP1 mRNA expression was restored. Acetylated histone H3 and H4 were found in promoter of SFRP1 gene in EC9706 cell line. Conclusion Hypermethylation of the SFRP1 promoter and histone acetylation can be found in ESCC cell line. The gene silencing of SFRP1 is related to promoter methylation and histone acetylation.

关 键 词：食管鳞癌 甲基化 分泌型卷曲相关蛋白1 组蛋白乙酰化 

分 类 号：R735.1[医药卫生—肿瘤]