原发性肝癌c-myc、c-N-ras癌基因甲基化异常及其表达

Studies on Methylation of c-myc and c-N-ras Genes and Expression of Oncogenes in Human Hepatocellular Carcinoma

目的探讨人肝细胞癌发生的分子生物学机理以及癌基因甲基化改变与其蛋白表达水平的关系。方法分别以限制性内切酶酶切结合Southern杂交法对人原发性肝癌c-myc及c-N-ras癌基因的甲基化状况进行分析，以免疫组化法研究p21ras及c-myc癌基因蛋白的表达情况。结果在12例c-N-ras及8例c-mycDNA低甲基化肝癌中分别有10及8例出现相应癌基因蛋白的高表达现象。结论提示低甲基化状态可通过导致癌基因的异常高表达而参与肝细胞癌的发生和发展。

Objcctivc DNA methylation belongs to the transcriptional genetic controlsystem regulating differentiation processes and gene expression. Abnormal DNA methylationmay influence tumor development by either enhancing gene expression or changing thechromatin structure. The aim of our study is to clarify the correlation between the aberrantmethylation patterns of specific oncogenes and their expression in hepatocellular carcinoma,so as to obtain information at the molecular level on the possible mechanism of hepa-tocarcinogenesis and also to provide further study. Methods The methylation patterns ofc-myc and c-N-ras 0ncogenes was measured by using the Southern blotting technique andHpall/Mspl restriction enzymes. At the same time, the expression of c-N-ras and c-mycgenes was studied by immunohistochemical examination- Results The results showed thathigher expressi0ns of c-N-ras and c-myc genes were detected in 73 %(11/15) and 83%(5/6) ofhepatocellular carcinomas with related oncogene hypomethylation. ConclusioD Itis suggested that DNA methylation is involved in hepatocarcinogenesis through enhance-ment of the expression of oncogenes.