Growth and differentiation of keratinocytes : Molecular and histological study

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Oral keratinocytes originate from basal cells, differentiate during migration to the surface, and finally are shed. Apoptosis occurs at the end of differentiation, but the precise relationship between terminal differentiation and apoptosis is not clear. In the present study, The bcl-2 proto-oncogene is a known inhibitor of apoptosis ; in normal human stratified squamous epithelium its expression is restricted to the basal cell layr. Bcl-xL was expressed in the basal cell and spinous cell layrs, and Bax was expressed in the spinous cell and granular cell layrs. In cultured keratinocytes, Bcl-xL was expressed under conditions of 0.1 mM calcium (low Ca2+) but disappeared under conditions of 1.0 mM calcium (high Ca2+) ; the latter induces keratinocyte differentiation. Bax was not expressed in keratinocytes with low Ca2+ but was expressed in cells with high Ca2+. And finally keratinocytes with high Ca2+ underwent apoptosis, which was detected by the TUNEL method and by 180-bp DNA fragmentation. To investigate the functional role of bcl-2 protein in the process of differentiation of oral keratinocytes, bcl-2 expression vector was transfected into SCC-25 cells, which normally undergo squamous cell differentiation in vitro while expressing specific differentiation markers, e.g., keratin10/11 and involucrin. In bcl-2 transfected SCC-25 cells, the expression of these differentiation markers was markedly suppressed.The bcl-2 proto-oncogene may play a critical role in opposing the commitment to terminal differentiation and apoptosis of oral keratinocytes. These results suggest that the process of terminal differentiation in gingival epithelium is a pathway to apoptosis.