Regulation of hepatocyte epidermal growth factor receptors by n-butyrate and dimethyl sulfoxide: sensitivity to modulation by the tumor promoter TPA.

n-Butyrate and dimethyl sulfoxide (DMSO) are known to promote differentiated characteristics in certain cells, including hepatocytes. We have previously reported that butyrate up-regulates the surface expression of hepatocyte epidermal growth factor (EGF) receptors and preserves a high-affinity receptor subpopulation. In the present study, culturing of hepatocytes with DMSO dose-dependently (0.5-2%) increased EGF binding and maintained a high-affinity binding component which was otherwise down-regulated during culturing. Although butyrate was more effective than DMSO in most experiments, the two agents caused qualitatively the same alteration in hepatocyte EGF receptor status. The high-affinity component of the EGF binding present in cells treated with butyrate or DMSO was reduced by treatment (10 nM-1 microM, 1 h) with the phorbol ester tumor promoter TPA, an activator of protein kinase C. Butyrate- or DMSO-treated hepatocytes were more susceptible to this response to TPA than were untreated hepatocytes. The present data indicate that in hepatocytes both butyrate and DMSO preserve a high-affinity EGF receptor subpopulation which is otherwise down-regulated during hepatocyte culture, and that this effect particularly comprises receptors that are sensitive to modulation by the tumor promoter TPA.