Antagonistic action of retinoic acid and teleocidin on the proliferation and epidermal growth factor binding of rat hepatoma cells.

Rat hepatoma cells were cultured in a medium with suboptimal concentration of fetal calf serum. In this low serum culture, retinoic acid inhibited the cell proliferation and enhanced the number of receptors for epidermal growth factor (EGF). On the contrary, teleocidin, a possible naturally occurring tumor promoter from Streptomyces, was a weak mitogen and inhibited EGF binding. A concurrent treatment of AH66 cells with these two compounds showed that they acted antagonistically. Retinoic acid inhibited the mitogenic action of teleocidin, while teleocidin suppressed the retinoic-acid enhancement of the number of EGF receptors. Retinoic acid could not prevent the alterations of the cell surface properties induced by a prolonged treatment with teleocidin. Furthermore, these two compounds appeared to be involved in the regulation of glycoprotein synthesis and the stimulation of cellular glycoprotein synthesis by retinoic acid was abolished by teleocidin. The present data suggest that retinoic acid selectively antagonizes the mitogenic action of teleocidin, and also indicate that the hepatoma cell cultures appear to prove a useful system for exploring the mechanisms of action of both retinoic acid and teleocidin.