DIFFERENCES IN THE STEADY-STATE LEVELS OF C-FOS, C-JUN AND C-MYC MESSENGER-RNA DURING MITOGEN-INDUCED LIVER GROWTH AND COMPENSATORY REGENERATION

The steady-state levels of c-fos, c-jun and c-myc messenger RNA were i nvestigated in rat liver tissue after proliferative stimuli of differe nt nature - namely, compensatory regeneration induced by partial hepat ectomy or carbon tetrachloride administration - and direct hyperplasia induced by four different hepatomitogens: lead nitrate, ethylene dibr omide, cyproterone acetate and nafenopin. We show here that whereas c- fos and c-jun expression increased soon after partial hepatectomy or c arbon tetrachloride administration, an increased expression of c-jun i n the absence of c-fos expression occurred during direct hyperplasia i nduced by lead nitrate and ethylene dibromide. When hyperplasia was in duced by cyproterone acetate and nafenopin, the mitogenic response of the liver was not associated with an increased expression of c-jun or c-fos, despite the fact that the timing of the cell cycle was similar to that observed after partial hepatectomy. Finally, when c-myc expres sion was analyzed, it was found that proliferative conditions associat ed with an increased expression of this gene were characterized by an increased expression of c-jun. On the contrary, the hyperplasia induce d by cyproterone acetate and nafenopin, which is characterized by a la ck of increase in the expression of c-fos and c-jun, was also not asso ciated with an increased c-myc expression. Similar results were obtain ed in these experiments with the mitogen nafenopin, a peroxisome proli ferator. In fact, liver hyperplasia induced by this compound was not p receded or accompanied by an increased expression of c-fos and c-myc. This study suggests that depending on the nature of the proliferative stimulus, an increased expression of c-fos, c-jun and c-myc may not be necessary for in vivo induction of liver cell proliferation.