乳腺癌雌激素受体α基因启动子甲基化及其蛋白表达关系.docVIP

乳腺癌雌激素受体α基因启动子甲基化及其蛋白表达关系 　 作者：布立敬，苏世振，李红智，林蓓蓓，张英俊 【摘要】 目的：检测乳腺癌雌激素受体α(estrogen receptorα， ERα)基因启动子区CpG岛甲基化状态，探讨乳腺癌ERα启动子甲基化与其蛋白表达及临床病理的关系。方法 ：采用免疫组化EnVisionTM二步法检测20例正常乳腺组织、44例乳腺癌组织ERα基因的表达，同时运用甲基化特异性PCR(Methylation-Specific PCR，MSP)及测序法分别检测ERα基因启动子A区和B区CpG岛的甲基化状态。结果：32例ERα阳性乳腺癌组织中，ERα启动子A区、B区甲基化率分别为28.2%和18.8%。12例ERα阴性乳腺癌组织中，ERα启动子A区、B区甲基化率分别为66.7%和58.3%。ERα阳性乳腺癌组、ERα阴性乳腺癌组、乳腺癌组的ERα启动子A、B区甲基化率均较正常组显著增高(P lt;0.05)；ERα阴性乳腺癌组的ERα启动子A、B区甲基化率较ERα阳性乳腺癌组均显著增高(P lt;0.05)。乳腺癌组织ERα表达与启动子区甲基化之间呈显著负相关。结论：乳腺癌组织ERα基因表达沉默与其启动子A区、B区CpG岛甲基化相关，后者有可能成为乳腺癌预后不良的分子检测指标。 【关键词】 乳腺肿瘤；雌激素受体；DNA甲基化；CpG岛；甲基化特异性PCR Abstract: Objective: To detect the methylation of CpG island in estrogen receptor alpha (ERα) gene promotor in breast cancer， and study the relationship among ERα gene promotor methylation，ERα expression，and the clinicopathological characteristics in breast cancer. Methods: The EnVisionTM two-step immunohistochemistry method was used to detect ERα gene expression in 20 cases of normal breast tissues and 44 cases of breast cancer tissues. The methylation of CpG island in ERα gene promotor region A and B was respectively detected using methylation-specific PCR (MSP) and sequencing. Results: In 32 cases of ERα positive breast cancer tissues， the methylation rates of ERα promotor region A and B were 28.2% and 18.8%，respectively; while in 12 cases of ERα negative breast cancer tissues， the methylation rates of ERα promotor region A and B were 66.7% and 58.3%，respectively. The methylation rates of ERα promotor region A and B in ERα negative breast cancer tissues， ERα positive breast cancer tissues and breast cancer tissues were significantly higher than that in normal breast tissues (P lt;0.05). The methylation rates of ERα negative breast cancer tissues were significantly higher than that of ERα positive cases (P lt;0.05). A negative relationship was indicated between ERα expression and the promotor methylation in breast cancer. Conclusion: The silencing of ERα gene expression