| 郭艳丽,周 珍,郭 炜.β-环连蛋白抑制基因2甲基化状态对贲门腺癌发生发展的影响及机制[J].中国肿瘤,2016,25(8):653-658. |
| β-环连蛋白抑制基因2甲基化状态对贲门腺癌发生发展的影响及机制 |
| Effect and Mechanism of Methylation of Dishevelled-Binding Antagonist of Beta-catenin 2 in Gastric Cardia Adenocarcinoma |
| 投稿时间：2015-11-11 |
| DOI：10.11735/j.issn.1004-0242.2016.08.A014 |
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| 中文关键词: β-环连蛋白抑制基因2 甲基化 贲门腺癌 |
| 英文关键词:dishevelled-binding antagonist of beta-catenin 2 methylation GCA |
| 基金项目:河北省自然基金（H2013206315）；河北省医学科学研究重点课题计划项目（20130543） |
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| 中文摘要: |
| 摘 要：［目的］ 检测贲门腺癌（gastric cardia adenocarcinoma，GCA）及相应癌旁组织中β-环连蛋白抑制基因2（dishevelled-binding antagonist of beta-catenin 2，DACT2）的表达情况及其临床意义，探讨引起基因表达异常的可能机制及对Wnt通路活化的影响。［方法］ 应用甲基化特异性PCR（methylation specific PCR，MSP）、RT-PCR分别检测河北省上消化道肿瘤高发区104例贲门腺癌及相应癌旁非肿瘤组织中DACT2基因的甲基化状态及mRNA的表达情况。应用免疫组织化学（IHC）检测β-catenin蛋白的表达。［结果］ 在104例贲门腺癌组织标本中，DACT2基因的甲基化发生率为60.6%(63/104)，明显高于癌旁非肿瘤组织(P<0.01)；且在发生该基因的甲基化的贲门腺癌标本中其mRNA表达及Wnt通路中心因子β-catenin的异常表达率均明显高于未发生该基因甲基化的贲门癌组织(P<0.01)；且该基因的甲基化状态与肿瘤患者的病理分级、临床分期、淋巴结转移和上消化道肿瘤家族史相关（P<0.05），而与肿瘤患者的年龄、性别无关（P>0.05）。［结论］ 基因启动子区的高甲基化状态是DACT2基因表达下调的机制之一，其低表达可引起Wnt/β-catenin信号传导通路的异常活化并在贲门腺癌的发生发展中发挥一定的作用。 |
| 英文摘要: |
| Abstract:［Purpose］ To explore the expression of and its clinical significance of dishevelled-binding antagonist of beta-catenin 2(DACT2) gene in gastric cardia adenocarcinoma(GCA) and adjacent tissues，and its possible mechanism of gene expression and the effect of Wnt pathway activation. ［Methods］ MSP and RT-PCR methods were applied respectively to examine the CpG methylation of the DACT2 gene promoter and its mRNA expression in 104 samples of GCA and corresponding adjacent non-concerous tissues of high risk area of upper digestive tract cancer in Hebei province. Immunohistochemistry was used to determine the expression of β-catenin protein. ［Results］ In 104 GC samples，the frequency of DACT2 methylation was 60.6%(63/104)，which was significantly higher than that in adjacent non-cancerous tissues(P<0.01). The expression of mRNA and the β-catenin，which was central factor of Wnt Signaling pathway，were significantly higher in methylated tissues than those in unmethylated tissues(Ｐ<0.01). Furthermore，DACT2 gene hypermethylation status correlated with pathological grading，clinical stage，lymph node metastasis，family history of upper digestive tract tumor，irrelevant with age and gender of tumor patients（P>0.05）. ［Conclusion］ Hypermethylation of the DACT2 gene was one of the mechanisms causing genes silencing in GCA，its low expression may cause the abnormal activation of Wnt/β-catenin signaling pathway and play a role in the development of GCA. |
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