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DLC1基因启动子甲基化和蛋白在散发性 乳腺癌及乳腺腺病良性病变组织中的表达[J]. 肿瘤防治研究, 2011, 38(04): 399-403. DOI: 10.3971/j.issn.1000-8578.2011.04.009
引用本文: DLC1基因启动子甲基化和蛋白在散发性 乳腺癌及乳腺腺病良性病变组织中的表达[J]. 肿瘤防治研究, 2011, 38(04): 399-403. DOI: 10.3971/j.issn.1000-8578.2011.04.009
Hypermethylation and Expression of DLCl Gene in Sporadic Breast Cancer and Breast Benign Lesions Tissues[J]. Cancer Research on Prevention and Treatment, 2011, 38(04): 399-403. DOI: 10.3971/j.issn.1000-8578.2011.04.009
Citation: Hypermethylation and Expression of DLCl Gene in Sporadic Breast Cancer and Breast Benign Lesions Tissues[J]. Cancer Research on Prevention and Treatment, 2011, 38(04): 399-403. DOI: 10.3971/j.issn.1000-8578.2011.04.009

DLC1基因启动子甲基化和蛋白在散发性 乳腺癌及乳腺腺病良性病变组织中的表达

Hypermethylation and Expression of DLCl Gene in Sporadic Breast Cancer and Breast Benign Lesions Tissues

  • 摘要: 目的探讨散发性乳腺癌(Sporadic breast cancer,SBC)、乳腺异型导管上皮增生(Breast atypital ductal hyperplasia,BADH)及乳腺腺病(Breast adenosis,BA)组织中肝癌缺失基因1 (Deleted in liver cancer-1,DLC1)启动子甲基化状态及其蛋白表达的关系,及DLCl基因异常的表遗传学作用与SBC发生的关系。方法采用甲基特异性聚合酶链反应(Methylation specific polrmerase chain reaction,MSP)研究42例SBC、14例BADH、20例BA组织及5例健康成人女性外周血淋巴细胞中DLC1 基因启动子甲基化状态并用免疫组织化学(EnVision法)研究SBC、BADH和BA中DLCl蛋白表达情况。结果5 例健康成人女性外周血淋巴细胞均为DLC1基因启动子甲基化阴性;SBC、BADH和BA中DCL1基因启动子CpG岛甲基化率分别为38.1%、35.7%和0。SBC和BADH的DLC1基因启动子甲基化阳性率显著高于BA;SBC与BADH之间DLC1基因启动子甲基化阳性率差异无统计学意义。SBC中DLC1蛋白表达阴性26例,表达下调16例,BADH 中DLC1蛋白阴性6例,表达下调8例;BA未见DLC1蛋白表达阴性或下调。16 例发生DLC1甲基化的 SBC,有14例蛋白表达阴性,2例表达下调。5例发生甲基化的BADH组织,3例蛋白表达阴性,2例表达下调。SBC、BADH的DLC1蛋白的阳性率显著低于BA;SBC的DLC1蛋白阳性率显著低于BADH。DLC1非甲基化组其蛋白表达的强度明显高于甲基化组,差异有统计学意义。结论DLC1基因启动子CpG岛甲基化是SBC发生过程中的早期事件, 是其蛋白表达下降乃至失活的重要原因,可能在乳腺癌变过程中起重要生物学作用。

     

    Abstract: ObjectiveTo study the methylation status of DLC1 gene promoter regions and the expression level of DLC1 protein in the development of sporadic breast cancer (SBC), and to research the epigenetics of aberrant DLC1 gene in SBC. Methods Methylation specific polymerase chain reaction (MSP) was used to study the methylation status of DLC1 promoter regions in 42 samples of SBC, 14 cases of breast atypital ductal hyperplasia (BADH), 20 cases of breast adenosis (BA) and 5 samples of peripheral lymphocytes from healthy adult women.The expression of DLC1 protein was detected by immunohistochemistry staining (EnVision method). Results We found DLC1 promoter methylation rate was 38.1% in SBC tissues.In BADH tissues,(35.7%) showed aberrant methylation of DLC1 gene promoter.While in the tissues of BA and 5 cases healthy adult women's peripheral lymphocytes, no methylation of DLC1 gene was found.In 42 cases of SBC, 26 cases (61.91%) showed loss expression of DLC1 protein and 16 cases (38.10%) showed reduction expression.In 14 BADH tissues, 6 cases (42.86%) showed negative expression of DLC1 protein, 8 cases (57.14%) showed reduced expression.No reduced or loss expression of DLC1 protein was found in BA tissues.In the 16 cases of DLC1 methylated SBC tissues, 14 cases showed no expression of DLC1 protein, another 2 cases showed weakly express DLC1 protein.In the 5 cases of DLC1 methylated BADH tissues, 3 cases negatively express, 2 cases showed reduced expression of DLC1 protein.Statistical analysis showed the methylation rates of DLC1 gene in SBC and BADH tissues were higher than that of BA.The difference in the three groups had statistical significance (P<0.01).While the methylation rates of DLC1 gene between SBC and BADH tissues were no difference.The expression rates of DLC1 protein in SBC and BADH tissues were lower than BA.And the expression rate of DLC1 protein in SBC is significantly lower than that of BADH.The positive intensities of DLC1 protein of DLC1 unmethylated group is higher than that of DLC1 methylated group(P<0.01). Conclusion The promoter methylation of DLC1 gene is an early event in the development of SBC and may contribute to the reduction or loss expression of DLC1 protein.The promoter methylation of DLC1 gene may play an important biological role in breast carcinogenesis.

     

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