Expression of c-fos and c-myc protooncogenes in an immortalized hepatocyte line harbouring SV40 T antigen and hGH as transgenes |
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Authors: | Karen I Hirsch-Ernst Dieter Paul Georg Friedrich Kahl Martin W Höhne |
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Institution: | (1) Institute of Pharmacology and Toxicology, University of Göttigen, Göttingen, Germany;(2) Department of Cell Biology, Fraunhofer-Institut for Toxicology, Hannover, Germany;(3) Institute of Medical Virology, University of Giessen Medical School, Frankfurter Strasse 107, D-6300 Giessen, Germany |
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Abstract: | 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. |
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Keywords: | growth factors SV40 T antigen hGH c-fos c-myc immortalized hepatocytes |
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