Runt相关转录因子3基因启动子区甲基化与乳腺癌雌激素受体阳性表达的相关性  

Correlation between the methylation status of Runx3 gene and positive expression of estrogen receptor in breast cancer

作　　者：闫战涛 高山[1] 吴瑕[1] 刘慧[1] 

机构地区：[1]徐州医学院病理学教研室,221002

出　　处：《中华病理学杂志》2015年第4期240-244,共5页Chinese Journal of Pathology

基　　金：江苏省卫生厅课题（H201020）;江苏省高校自然科学基金（10KJB310014）

摘　　要：目的分析Runt相关转录因子3（Runx3）基因启动子区高甲基化与雌激素受体（ER）表达的相关性，探讨其在ER阳性乳腺癌中的作用。方法用Westernblot和逆转录一聚合酶链反应检测乳腺癌细胞MCF7、SKBR3和正常乳腺上皮细胞MCFl0A中Runx3蛋白和mRNA的表达，采用免疫组织化学（SP法）检测113例乳腺癌组织中ER和Runx3蛋白表达，用甲基化特异性PCR检测MCF7、SKBR3、MCFIOA及113例乳腺癌组织中Runx3基因启动子区甲基化状态，分析113例乳腺癌组织中Runx3基因启动子区甲基化与ER、Runx3蛋白表达的关系及其与不同亚型乳腺癌临床病理参数的相关性。结果（1）MCFIOA中Runx3蛋白阳性表达、Runx3mRNA有表达，MCF7和SKBR3为Runx3蛋白阴性、Runx3mRNA无表达；Runx3基因启动子区在MCF10A和SKBR3中呈非甲基化状态，在MCF7中为高甲基化状态。（2）Runx3蛋白在ER阳性和ER阴性乳腺癌组织中阳性率分别为26．5％（18／68）、66．7％（30／45）（P〈0．05）；Runx3基因启动子高甲基化率在ER阳性和ER阴性乳腺癌组织中分别为82．4％（56／68）、22．2％（10／45，P〈0．05）。（3）ER阳性乳腺癌中，Runx3基因启动子高甲基化与患者的临床分期呈正相关（OR=5．84，P=0．015）。结论乳腺癌组织中Runx3启动子高甲基化可能与ER阳性表达有关，Runx3启动子高甲基化主要见于ER阳性乳腺癌组织。Runx3基因启动子甲基化检测可能为乳腺癌患者（特别是ER阳性患者）临床分期或预后的判断提供参考和依据。Objective To investigate the relationship between hypermethylation of Runx3 gene promoter and estrogen receptor （ER） and the implications of Runx3 gene promoter hypermethylation in ER positive breast cancer. Methods Western blot and RT-PCR were used to detect the protein and mRNA expression of Runx3 gene in breast cancer cell lines （ MCF7 and SKBR3 ） and normal breast epithelium cell line （MCFIOA）. Immunohistochemical SP method was used to detect the expression of ER and Runx3 proteins in 113 tissue samples of breast cancer. Moreover, methylation specific PCR was used to detect RUN3 promoter methylation in cell lines MCFT, SKBR3, MCF10A and 113 tissue samples of breast cancer. Results Of the 3 cell lines, Runx3 protein and mRNA were detectable in MCF10A, but were absent in MCF7 and SKBR3. MCF7 had a high methylation status at Runx3 promoter, in contrast, MCF10A and SKBR3 showed unmethylated RUN3 promoter. Among the 113 cases of breast cancer, 68 cases were ER positive and 45 were negative. The positive rates of Runx3 protein expression in ER positive and negative tumors were 26. 5% （ 18/68 ） and 66.7% （ 30/45 ） , respectively （ P 〈0. 05 ） . Runx3 promoter hypermethylation was seen in 82.4% （56/68） of ER positive breast cancer cases and 22.2% （ 10/45 ） of ER negative ones （ P 〈 0.05 ）. Among 68 cases of ER positive cases, Runx3 promoter hypermethylation was positively correlated with the clinical tumor stage （ OR=5.84, P 〈 0. 05 ）. Conclusions Runx3 genepromoter hypermethylation is present mainly in the ER positive breast cancers. Testing of Runx3 promoter methylation may provide additional reference for clinical stage and prognosis of breast cancer patients, especially in those with ER positive tumors.

关 键 词：乳腺肿瘤 核心结合因子α3亚基 DNA甲基化 受体 雌激素 

分 类 号：R737.9[医药卫生—肿瘤]