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 o f the c-fos proto-oncogene in keratinocyte differentiation. To further elucidate this question we have used keratinocyte and skin culture mo dels to study in vitro regulation of c-fos expression and attempted to correlate it with the keratinocyte maturation process. Our results sh ow that c-fos expression is prolonged in keratinocyte monolayers both at the mRNA and protein level. Extracellular calcium which stimulate k eratinocyte differentiation is able to induce c-fos expression in the presence of growth factors. However this c-fas expression cannot be ma intained by these factors as seen in normal human skin in vivo. Conver sely, spontaneous expression of c-fos can be seen in reconstituted ski n when the neo-epidermis has completed its differentiation. All these data strongly support a role of c-fos as a switch between the early an d late phases of keratinocyte differentiation allowing them to be defi nitively committed to their elimination process. Additionally, a diffe rential regulation of c-fos seems to exist between keratinocyte cultur e and reconstituted epidermis, suggesting that tissular and serum fact ors are involved in the prolonged c-fos expression observed in human e pidermis.