微信公众号

官网二维码
中国癌症防治杂志

中国癌症防治杂志 ›› 2015, Vol. 7 ›› Issue (2): 80-84.doi: 10.3969/j.issn.1674-5671.2015.02.03

• 基础研究 • 上一篇    下一篇

大鼠肝癌组织中DLC1、ASC、p16和DLK1基因甲基化状态与肝癌的关系

  

  1. 广西肿瘤防治研究所实验研究部；广西医科大学研究生学院；广西医科大学第一附属医院肿瘤内科
  • 出版日期:2015-04-25 发布日期:2015-05-14
  • 通讯作者: 杨春
  • 基金资助:

    广西自然科学基金资助项目（2012GXNSFAA053167）；广西自然科学基金青年基金资助项目（2014GXNSFBA118193）；广西医科大学青年科学基金资助项目（GXMUYSF201218）

Analysis of DLC1，ASC，p16 and DLK1 gene methylation in a rat model of liver cancer

  • Online:2015-04-25 Published:2015-05-14
  • Contact: cxl_yang@163.com

PDF (PC)

726

赞

摘要：

目的 探讨大鼠肝癌组织中DLC1、ASC、p16和DLK1基因启动子区甲基化状态与肝癌发生的关系。方法 55只Wistar雄性大鼠随机分为黄曲霉毒素B1（Aflatoxin B1，AFB1）实验组（35只）和空白对照组（20只），用AFB1诱发大鼠肝癌并建立大鼠实验动物肝癌模型。用甲基化特异性PCR（MS-PCR）技术和琼脂糖凝胶电泳方法检测大鼠肝癌组织及正常肝脏组织中DLC1、ASC、p16和DLK1基因启动子区的甲基化情况，分析4个基因的甲基化状态与肝癌发生的关系。结果 在实验第52周可见大鼠肝脏发生典型的肝癌病理学改变，实验诱发大鼠肝癌模型制作成功。MS-PCR技术检测显示在大鼠肝癌组织中DLC1、ASC、p16和DLK1基因启动子区的甲基化率分别为83.3%、93.3%、86.7%和10.0%，在大鼠正常肝脏组织中的甲基化率分别为14.3%、35.7%、21.4%和85.7%，二者比较差异均有统计学意义（P均<0.05）。琼脂糖凝胶电泳法检测显示4种基因甲基化均为阳性。结论 大鼠肝癌组织中DLC1、ASC、p16基因启动子区高度甲基化，DLK1基因启动子呈低甲基化水平，提示 DLC1、ASC、p16和DLK1基因启动子区的异常甲基化与大鼠肝癌发生的关系密切。

关键词: 肝肿瘤, DLC1, ASC, p16, DLK1, 基因, 甲基化

Abstract:

Objective To study the potential association between liver cancer and methylation of the promoters of the genes DLC1，ASC，p16，and DLK1. Methods Primary hepatocellular carcinoma（PHC）was induced in 35 Wistar rats by injection of AFB1. Another group of 20 rats received no drug and served as a negative control. At week 52，all rats were killed and tissue samples were harvested and analyzed for histopathology. Methylation-specific PCR was used to analyze methylation of the promoters of the genes DLC1，ASC，p16，and DLK1 in rat liver in both groups. Results AFB1-induction of PHC led to the expected pathological changes in rat liver. Methylation rates of DLC1，ASC，p16 in liver tissue were significantly higher in rats with PHC（83.3%，93.3%，86.7%，respectively） than in control rats （14.3%，35.7%，21.4%；all P<0.05），whereas the opposite was true for methylation rates of DLK1 （10.0% vs 85.7%，P<0.05）. Conclusion PHC may be associated with upregulation of DLC1，ASC，and p16 methylation，as well as downregulation of DLK1 methylation. Thus，aberrant methylation of DLC1，ASC，p16 and DLK1 may contribute to PHC onset and progression.

Key words: Liver neoplasm, DLC1, ASC, p16, DLK1, Gege, Methylation