Roles of oncogenes and growth factor receptors in hepatocarcinogenesis

分析肝癌的癌基因和生长因子受体。在PLC/ORF/5和Hep G2人肝癌源性细胞系中，使用<125D> - 1标记配体进行放射受体检测发现表皮生长因子（EGF）的高结合能力和胰岛素的低结合能力。胰岛素样生长因子- i （IGF-I）在PLC/PRF/5细胞中的结合明显高于Hep G2细胞。对两株细胞株的DNA和mRNA进行斑点杂交分析，结果显示12种癌基因均有表达。在肝癌细胞中没有特异性表达的癌基因。EGF确实增强了肝癌细胞的DNA合成，但癌基因的表达没有改变。我们使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的癌基因产物和生长因子相关蛋白。10个肝癌组织和2个肝癌细胞系中有4个的细胞膜上有EGF受体染色。癌变部位的染色强度大于非癌变部位。myc产物在2 / 10的肝癌和2个细胞系的细胞核中呈阳性。ras产物在两种细胞系细胞质中呈阳性，在肝癌组织中无阳性。EGF和TGF均未阳性。由此可见，许多致癌基因可能参与了肝癌的多步骤发生。

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.