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.
Gladhaug
I P
IP
Department of Pharmacology, School of Medicine, University of Oslo, Norway.
Refsnes
M
M
Christoffersen
T
T
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002087:Butyrates; D020148:Butyric Acid; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide