Hirsch-Ernst K I, Paul D, Kahl G F, Höhne M W
Institute of Pharmacology and Toxicology, University of Göttingen, Germany.
Transgenic Res. 1993 Mar;2(2):101-8. doi: 10.1007/BF01969383.
A clonal hepatocyte line (FMH-202-2), derived from livers of fetal transgenic mice harbouring human growth hormone (hGH) and SV40 T antigen as transgenes, was used in the investigation of protooncogene expression involved in liver-specific growth control and/or in hepatocellular transformation. In this model system, representing an immortalized, yet untransformed phenotype, the transgenes hGH and SV40 T antigen were expressed constitutively. The c-fos protooncogene was induced by incubation with insulin, epidermal growth factor (EGF) and insulin-like growth factor (IGF-I) in a transient manner comparable to its expression in primary murine hepatocytes. Elucidation of second messenger mechanisms demonstrated that c-fos induction by hepatotrophic growth factors was not mediated by protein kinase C. In contrast to primary hepatocytes, the c-myc protooncogene exhibited a constitutive expression pattern which was independent of growth factor stimulation. These results indicate that apart from hGH and SV40 T antigen, c-myc may play a role in cellular immortalization, but that constitutive expression of these genes, even in combined coexpression, does not suffice to induce the transformed phenotype.
一种克隆肝细胞系（FMH - 202 - 2），源自携带人生长激素（hGH）和SV40 T抗原作为转基因的胎儿转基因小鼠肝脏，用于研究参与肝脏特异性生长控制和/或肝细胞转化的原癌基因表达。在这个代表永生化但未转化表型的模型系统中，转基因hGH和SV40 T抗原持续表达。c - fos原癌基因通过与胰岛素、表皮生长因子（EGF）和胰岛素样生长因子（IGF - I）孵育而被短暂诱导，其方式与在原代小鼠肝细胞中的表达相当。对第二信使机制的阐明表明，肝细胞生长因子对c - fos的诱导不是由蛋白激酶C介导的。与原代肝细胞不同，c - myc原癌基因表现出一种与生长因子刺激无关的组成型表达模式。这些结果表明，除了hGH和SV40 T抗原外，c - myc可能在细胞永生化中起作用，但这些基因的组成型表达，即使是联合共表达，也不足以诱导转化表型。
