| 周 徽，胡光胜，曾 斌，廖爱军.WIF-1、DKK基因启动子甲基化对COLO 320、.[J].中南医学科学杂志.,2015,43(4):383-387. |
| WIF-1、DKK基因启动子甲基化对COLO 320、 |
| Hypermethylation of WIF-1 and DKK Gene Family on the β-catenin Phosphorylation in Colorectal Adenocarcinoma Cell Lines COLO 320 and HT-29 |
| 投稿时间：2015-04-30 |
| DOI： |
| 中文关键词: Wnt/β-catenin信号通路 甲基化 结直肠癌 表观遗传学 |
| 英文关键词:WNT/β-catenin signaling pathway hypermethylation colorectal adenocarcinoma epigenetics |
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| 中文摘要: |
| 目的 探讨Wnt抑制性基因甲基化对结直肠癌细胞株Wnt/β-catenin信号通路的影响。 方法 使用甲基特异性PCR和逆转录实时定量PCR方法，分别检测结直肠癌细胞株COLO 320、HT-29及正常细胞株CCD-18Co中WIF-1、DKK-1、DKK-3的启动子CpG岛甲基化、mRNA水平，和测定β-catenin蛋白磷酸化情况，并观察5-氮杂-2′-脱氧胞苷（5-aza-dC）去甲基化对各指标的影响。 结果 COLO 320细胞的DKK-1及DKK-3 mRNA水平明显降低、甲基化程度高；HT-29细胞的DKK-3、WIF-1 mRNA水平低、甲基化程度高；两个肿瘤细胞株的β-catenin蛋白总量均明显增高，且主要为非磷酸化的状态。5-aza-dC可减少这些指标的改变。 结论 抑制性基因甲基化调节的Wnt/β-catenin通路的异常激活，可能在结直肠癌的形成中有重要作用。在不同的肿瘤细胞株之间、不同Wnt抑制基因的甲基化程度存在差异；该领域的深入研究有助于开发出新的治疗药物。 |
| 英文摘要: |
| Objective To reveal the the effect of methylated inhibitory genes on Wnt/β-catenin pathway in colorectal adenocarcinoma cell lines. Methods With colorectal adenocarcinoma cell lines COLO 320,HT-29 and normal colorectal cell line cCCD-18Co,methylation status of CpG island in promotor of WIF-1,DKK-1 and DKK-3 genes were determined by methylation specific PCR （MSP）,and mRNA levels of these genes were quantified by real-time RT-PCR,and phosphorylated β-catenin were semi-quantified by Western blot.Effect of DNA-demethylating agent 5-aza-2′-deoxycytidine （5-aza-dC） treatment were also evaluated. Results DKK-1and DKK-3 mRNA decreased accompanied with hypermethylation status of the CpG islands in COLO 320,while DKK-3 and WIF-1 mRNA decreased accompanied with hypermethylation in HT-29.Total β-catenin increased significantly while phosphorylated β-catenin declined in both cell lines.5-aza-dC ameliorated these aberrant parameters partially. Conclusion The aberrant activation of Wnt/β-catenin pathway mediated by the hypermethylation of WIF-1 and DKKs genes may contribute to the oncogenesis of colorectal adenocarcinoma,while the methylation level of different Wnt inhibitory genes varied in colorectal cancer cell lines.Further research on this field will prompt the development of new therapies targeting the methylation process. |
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