Comparative analysis of cellular and tissular expression of c-fos in human keratinocytes: evidence of its role in cell differentiation.
Recent studies on normal and pathological skin have suggested a role of the c-fos proto-oncogene in keratinocyte differentiation. To further elucidate this question we have used keratinocyte and skin culture models to study in vitro regulation of c-fos expression and attempted to correlate it with the keratinocyte maturation process. Our results show that c-fos expression is prolonged in keratinocyte monolayers both at the mRNA and protein level. Extracellular calcium which stimulate keratinocyte differentiation is able to induce c-fos expression in the presence of growth factors. However this c-fos expression cannot be maintained by these factors as seen in normal human skin in vivo. Conversely, spontaneous expression of c-fos can be seen in reconstituted skin when the neo-epidermis has completed its differentiation. All these data strongly support a role of c-fos as a switch between the early and late phases of keratinocyte differentiation allowing them to be definitively committed to their elimination process. Additionally, a differential regulation of c-fos seems to exist between keratinocyte culture and reconstituted epidermis, suggesting that tissular and serum factors are involved in the prolonged c-fos expression observed in human epidermis.
Basset-Séguin
N
N
Laboratoire de Dermatologie Moléculaire, CNRS UMR 9942, Montpellier, France.
Demoly
P
P
Moles
J P
JP
Tesnières
A
A
Gauthier-Rouvière
C
C
Richard
S
S
Blanchard
J M
JM
Guilhou
J J
JJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016762:Genes, fos / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D007328:Insulin; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D004815:Epidermal Growth Factor; D002118:Calcium