Transient expression of c-fos and constant expression of c-myc in freshly isolated and cultured normal adult rat hepatocytes.

A rapid and transient induction of the c-fos transcript followed 4 hr later by long-term increase in the c-myc transcript was observed after disruption of the liver tissue with collagenase or EDTA perfusion and after in vitro detachment of the cell-sheet of liver cells in culture. This increase of c-fos and c-myc transcripts could result from both an increased gene transcription and a stabilization of the corresponding mRNAs, as suggested by the effects of cycloheximide and actinomycin D. This increase was dependent on the extent of cell dissociation and isolation and was not the effect of dissociating agents. These findings strongly argue in favor of the role of cell-cell interactions in the induction of these two oncogenes. They are consistent with observations made on injured cells, or cells entering the G1 phase or undergoing differentiation since all these situations involve morphological changes and cell-cell contact modifications. In addition, evidence is given for a constant expression of the c-myc gene in normal hepatocytes maintained in non-proliferative primary culture. This unexpected c-myc maintenance raises the question of the role of this oncogene in hepatocyte differentiation.