The steady-state levels of c-fos, c-jun and c-myc
messenger RNA were investigated in rat liver tissue after proliferative stimuli of different nature-namely, compensatory regeneration induced by partial
hepatectomy or
carbon tetrachloride administration-and direct
hyperplasia induced by four different hepatomitogens:
lead nitrate,
ethylene dibromide,
cyproterone acetate and
nafenopin. We show here that whereas c-fos and c-jun expression increased soon after partial
hepatectomy or
carbon tetrachloride administration, an increased expression of c-jun in the absence of c-fos expression occurred during direct
hyperplasia induced by
lead nitrate and
ethylene dibromide. When
hyperplasia was induced 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 expression was analyzed, it was found that proliferative conditions associated with an increased expression of this gene were characterized by an increased expression of c-jun. On the contrary, the
hyperplasia induced by
cyproterone acetate and
nafenopin, which is characterized by a lack of increase in the expression of c-fos and c-jun, was also not associated with an increased c-myc expression. Similar results were obtained in these experiments with the
mitogen nafenopin, a peroxisome proliferator. In fact, liver
hyperplasia induced by this compound was not preceded 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.