Roles of oncogenes and growth factor receptors in hepatocarcinogenesis

对肝癌中的癌基因和生长因子受体进行了分析。~lt；125d&gt；I标记配体的放射受体分析表明，PLC/ORF/5和Hep G2人肝癌细胞系具有高结合表皮生长因子(EGF)的能力和低结合胰岛素的能力。PLC/PRF/5细胞的胰岛素样生长因子-I(IGF-I)结合率明显高于Hep G2细胞。DNA和mRNA的斑点杂交分析显示，所测试的12个癌基因均有表达。未见癌基因在肝癌细胞中特异表达。EGF对肝癌细胞DNA合成有促进作用，但癌基因表达无明显变化。我们用免疫组织化学方法检测了手术切除的肝癌组织和两种肝癌细胞系中的癌基因产物和生长因子相关蛋白。EGF受体在10例肝癌组织和2株肝癌细胞系中有4例表达于细胞膜。癌变部分染色强度高于非癌变部分。Myc产物在2/10的肝癌细胞核和两种细胞系中均呈阳性表达。Ras产物在两种细胞系的胞浆中呈阳性表达，而在肝癌组织中未见表达。表皮生长因子和转化生长因子均为阳性。由此可见，许多癌基因可能参与了肝癌的多步发生。

Oncogenes and growth factor receptors were analyzed in hepatomas. Radioreceptor assays using <125D>I- labeled ligand revealed the high binding capacity of epidermal growth factor ( EGF ) and the low binding of insulin in PLC/ORF/5 and Hep G2 human hepatoma-derived cell lines. The binding of insulin-like growth factor-I ( IGF-I ) in PLC/PRF/5 cells was significantly higher than that in Hep G2 cells. Dot blot analyses of DNA and mRNA of the two cell lines showed expressions of all 12 oncogenes tested. There was no oncogene specifically expressed in hepatoma cells. EGF did enhanced the DNA synthesis of the hepatoma cells, but the oncogene expression did not change. We examined the oncogene products and growth factor-related proteins in surgically resected hepatoma tissues and the two hepatoma cell lines using an immunohistochemical method. EGF receptor was stained in the cell membrane of 4 out of 10 hepatoma tissues and the two hepatoma cell lines. The staining intensity was stronger in the cancerous portion than in the non-cancerous portion. The myc product was positive in the nuclei of 2 out of 10 hepatomas and in the two cell lines. The ras product was positive in the cytoplasm of the two cell lines, not in the hepatoma tissues. Neither EGF nor TGF was positive. From these, many oncogenes may be involved in the multistep hepatocarcinogenesis.