Modulation of epidermal growth factor and keratinocyte growth factor effects on human keratinocyte growth by protein kinase C inhibitor, GF 109203X: comparison to fibroblast growth modulation.
In this study, epidermal growth factor (EGF), 20 ng/ml, and keratinocyte growth factor (KGF), 10 ng/ml, were able to stimulate human keratinocyte growth only in presence of GF 109203X 1 microM, a selective PKC inhibitor. This suggests that PKC negatively controls keratinocyte growth in response to EGF and KGF. On the other hand, EGF and KGF have no significant effect on PKC activity. In contrast, in human fibroblasts, EGF stimulated fibroblast growth in the presence or not of GF 109203X. Thus, EGF seems to stimulate fibroblast growth in a PKC independent manner. Moreover, EGF didn't modify significantly PKC activity in fibroblasts. KGF had no effect on fibroblasts. These results show differences in the interconnections between PKC and EGF transduction pathway in the modulation of human keratinocyte and fibroblast growth. Moreover, they especially demonstrate that PKC would negatively control human keratinocyte growth in response to EGF and also to KGF.
Unité INSERM 312, Hôpital Henri Mondor, Créteil, France.
R
R
Le Panse
V
V
Mitev
C
C
Lebreton
B
B
Coulomb
D000328:Adult; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012867:Skin / Q000166:cytology
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D007211:Indoles; D008301:Maleimides; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; C070515:bisindolylmaleimide I