Comparative analysis of cellular and tissular expression of c-fos in human keratinocytes: evidence of its role in cell differentiation

Basset-Seguin, N.; Demoly, P.; Moles, J. P.; Tesnieres, A.; Gauthier-Rouviere, C.; Richard, S.; Blanchard, J. M.; Guilhou, J. J.


1994-03 / vol 9 / pages 765-71


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.

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Humans; Animals; Cell Differentiation/*genetics; Cells, Cultured; Cattle; Calcium/pharmacology; Epidermal Growth Factor/pharmacology; Genes, fos/*physiology; Insulin/pharmacology; Keratinocytes/drug effects/*metabolism; Pituitary Gland/metabolism; Proto-Oncogene Proteins c-fos/genetics/physiology; Skin/cytology/drug effects/metabolism

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