乳腺癌雌激素受体α基因启动子甲基化与其蛋白表达的关系

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1、乳腺癌雌激素受体α基因启动子甲基化与其蛋白表达的关系作者：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(estrogenreceptorα，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-SpecificPCR，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

2、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<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<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

3、激素受体；DNA甲基化；CpG岛；甲基化特异性PCR13Abstract:Objective:TodetectthemethylationofCpGislandinestrogenreceptoralpha(ERα)genepromotorinbreastcancer，andstudytherelationshipamongERαgenepromotormethylation，ERαexpression，andtheclinicopathologicalcharacteristicsinbreastcancer.Methods:TheEnVisionTM

4、two-stepimmunohistochemistrymethodwasusedtodetectERαgeneexpressionin20casesofnormalbreasttissuesand44casesofbreastcancertissues.ThemethylationofCpGislandinERαgenepromotorregionAandBwasrespectivelydetectedusingmethylation-specificPCR(MSP)andsequencing.Results:In32casesofERαpositiv

5、ebreastcancertissues，themethylationratesofERαpromotorregionAandBwere28.2%and18.8%，respectively;whilein12casesofERαnegativebreastcancertissues，themethylationratesofERαpromotorregionAandBwere66.7%and58.3%，respectively.ThemethylationratesofERαpromotorregionAandBinERαnegativebreastca

6、ncertissues，ERαpositivebreastcancertissuesandbreastcancertissuesweresignificantlyhigherthanthatinnormalbreasttissues(P<0.05).ThemethylationratesofERαnegativebreastcancertissuesweresignificantlyhigherthanthatofERαpositivecases(P<0.05).Anegativerelationshipwas13indicatedbetwe

7、enERαexpressionandthepromotormethylationinbreastcancer.Conclusion:ThesilencingofERαgeneexpressionissuggestedtobesignificantlyrelatedwiththemethylationofCpGislandintheERαpromotorregioninbreastcancer.ThemethylationofCpGislandmaybecomethemolecularmarkerindicatingbadprognosisofbreast

8、cancer.Keywords:breasttumor；estrogenrece