Expression of c-fos and c-myc protooncogenes in an immortalized hepatocyte line harbouring SV40 T antigen and hGH as transgenes.
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.
Institute of Pharmacology and Toxicology, University of Göttingen, Germany.
K I
KI
Hirsch-Ernst
D
D
Paul
G F
GF
Kahl
M W
MW
Höhne
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D007328:Insulin; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone