首页> 中文期刊> 《山西医药杂志》 >散发性乳腺癌中DNA甲基转移酶1与乳腺癌易感基因1基因甲基化和蛋白表达的相关性

散发性乳腺癌中DNA甲基转移酶1与乳腺癌易感基因1基因甲基化和蛋白表达的相关性

         

摘要

Objective To discuss the expression of DNA methyltransferases (DNM T )1 and the correlation between DNM T1 and BRCA1 protein expression ,BRCA1 gene promoter methylation in sporadic breast cancer . Methods By immunohistochemical staining ,the expression of DNMT1 protein was detected in 182 cases of spo‐radic breast cancer and 30 cases of breast fibroadenoma tissue .Using MSP‐PCR ,BRCA1 gene promoter methyla‐tion status was detected in 97 cases of sporadic breast cancer .The results were analyzed with χ2 test ,Fisher exact test and Spearman rank correlation .Results Compared with breast fibroadenoma ,the level of DNMT1 protein ex‐pression in breast cancer tissues is significantly increased ( P =0 .013);DNM T1 protein have a higher expression in the tissues with lymph node metastasis ( P=0 .014).The expression of DNMT1 protein and BRCA1 gene pro‐moter methylation had a significant positive correlation ( r =0 .349 ,P <0 .01);the expression of DNMT1 can shorten the patients′s OS and DFS .Conclusion The higher expression level of DNMT1 protein in sporadic breast cancer was associated with invasion and metastasis of tumor ;and DNM TI might catalyze the methylation of BRCA1 ,thus down‐regulated the expression of BRCA1 protein ,which might be the mechanism leading to poor prognosis in patients with breast carcinoma .It is prompted that the inhibition of DNM T 1 may be beneficial to the treatment of breast cancer.%目的:本研究通过检测DNA甲基转移酶(DNM T )1在散发性乳腺癌中的表达,分析DNM T1与乳腺癌易感基因(BRCA)1蛋白表达及基因启动子甲基化状态的相关性,以探讨DNMT1在散发性乳腺癌中的临床意义。方法应用免疫组织化学法检测182例散发性乳腺癌与30例乳腺纤维腺瘤组织中DNM T1蛋白的表达水平,应用甲基特异化聚合酶链反应(PCR)检测97例散发性乳腺癌组织中BRCA1基因启动子区甲基化状态,采用χ2检验、Fisher确切概率法、Spearman等级相关进行统计学分析。结果与乳腺纤维腺瘤相比,乳腺癌组织中DNM T1蛋白表达水平均显著增高( P =0.013);在发生淋巴结转移的组织中DNM T1蛋白表达量增多( P =0.014);用甲基特异化PCR法检测97例乳腺癌标本中BRCA1蛋白基因启动子区甲基化率为19.6%;DNM T1蛋白的表达与BRCA1基因启动子区甲基化呈正相关( r = 0.349,P <0.01);BRCA1和DNM T1阳性表达有降低患者总体生存期(OS)( P =0.059,P =0.041)和无病生存期(DFS)( P =0.054,P =0.026)的趋势。结论乳腺癌中DNM T1蛋白高表达与肿瘤侵袭转移相关,并且可能存在DNM T1催化BRCA1基因甲基化,从而下调BRCA1蛋白表达,进而导致乳腺癌患者预后不良的机制,提示抑制DNM T1可能利于乳腺癌的治疗。

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