【摘要】 目的:探讨BRCA1基因启动子甲基化对BRCA1蛋白表达的影响,及与散发性乳腺癌发病之间的关系。方法:甲基化特异性PCR(MSP)法检测51例散发性乳腺浸润导管癌和10例乳腺良性组织的BRCAl基因启动子甲基化状态,SP法检测BRCA1蛋白表达水平。结果:10例乳腺良性组织中均未检测到BRCA1启动子的异常甲基化,BRCA1蛋白在细胞核均阳性表达,其中70%(7/10)为强阳性表达。在51例散发性乳腺浸润性导管癌组织中检测到7例(13.73%)BRCA1启动子发生异常甲基化,其余44例(86.27%)未检测到BRCA1启动子甲基化。7例BRCA1启动子甲基化的组织均未见BRCA1蛋白细胞核阳性表达(0/7),仅有1例BRCA1蛋白细胞质表达;44例未检测到BRCA1启动子甲基化的浸润性导管癌中,30例(68.18%)BRCA1蛋白在细胞核阳性表达,14例(31.82%)BRCA1蛋白在细胞核阴性表达。BRCA1启动子甲基化与BRCA1蛋白核低表达密切相关,χ2=11.959 1,P=0.000 5;BRCA1蛋白的表达在乳腺良性组织与癌组织之间差异有统计学意义,χ2=4.587 9,P=0.032。结论:乳腺癌易感基因BRCA1启动子甲基化可抑制BRCA1蛋白表达,并影响其参与散发性乳腺癌的发生发展过程。更多还原

【Abstract】 OBJECTIVE:To investigate the effects of the aberrant hypermethylation of BRCA1 promoter on the expression of BRCA1 protein,and relate to the happening and development of sporadic breast cancer.METHODS: For selected 51 sporadic breast infiltrating ductal carcinoma tissues and 10 benign breast tissues,the methylation status of BRCA1 promoter was analyzed by methylation specific PCR(MSP),and the expression level of BRCA1 protein was detected by immunohistochemistry(IHC).RESULTS: There were unmethylation of BRCA1 promoter in 10 tissues of benign breast tissues,and the positive expression of BRCA1 protein in the nuclei.In 51 sporadic breast infiltrating ductal carcinoma tissues,7(13.73%) carcinoma tissues had hypermethylation of BRCA1 promoter,44 cases had unmethylation of BRCA1 promoter,and the proportion was 86.27%(44/51).For all of the 7 hypermethylated cases,the expression of BRCA1 protein was not detected in the nuclei(0/7),for 1 of 7 cases the expression of BRCA1 protein was detected in the cytoplasma.For the 44 unmethylated tissues,the nuclei positive expression of BRCA1 protein was found in 30 tissues(68.18%),the nuclei negative expression of BRCA1 protein in 14 tissues(31.82%).The methylation of BRCA1 promoter had significant relationship with the expression grade of BRCA1 protein,χ2=11.959 1,P=0.000 5;the expression of BRCA1 had a significant difference between the benign breast tissues and the sporadic breast infiltrating ductal carcinoma tissues,χ2=4.587 9,P=0.032.CONCLUSION: Promoter hypermethylation of BRCA1 inhibits the expression of BRCA1 protein and influences its participation in the happening and development of sporadic breast cancer.更多还原