Sequential expression of c-oncs in regenerating liver.

点击翻译按钮获取中文摘要

In regenerating liver, cellular oncogenes such as c-fos and c-myc are expressed sequentially. To analyze the molecular mechanism of gene expression in vitro, we tried to develop cell culture system in which oncogenes were expressed sequentially. Human hepatocytes and hepatoma cells were growth arrested by culturing in serum-free medium and then stimulated with serum. Transient and sequential increases in c-fos and c-myc mRNAs were observed which resembled the in vivo liver regeneration after partial heaptectomy. Using these in vitro culture system, we analyzed the effect of various growth factors and growth inhibitors. Both EGF and PDGF stimulated the sequential expression of c-fos and c-myc gene. Tumor promoter teleocidin and butyrate inhibited the growth of the hepatoma cells and the expression of c-myc. The change of c-myc expression was not associated with the alteration of the higher structure of c-myc gene as measured by DNase I hypersensitivity. On the other hand, novobiocin, a topoisomerase II inhibitor, reduced the DNase I sensitivity of c-myc without reducing c-myc mRNA. These results may suggest that the analysis of transcription factors by gel retardation assay using specific promoter of c-oncs is necessary to provide further information about the expression of c-oncs.