EXPRESSION OF MAD, AN ANTAGONIST OF MYC ONCOPROTEIN FUNCTION, IN DIFFERENTIATING KERATINOCYTES DURING TUMORIGENESIS OF THE SKIN

The Myc oncoprotein is associated with cell proliferation and is often down-regulated during cell differentiation. The related Mad transcrip tion factor, which antagonises Myc activity, is highly expressed in ep idermal keratinocytes. Mad also inhibits cell proliferation in vitro. To study Mad expression in keratinocyte proliferation and differentiat ion; we have analysed Mad RNA expression in regenerating and hyperprol iferative epidermal lesions and epidermal tumours of varying degrees o f differentiation using the RNA in situ hybridisation and RNAase prote ction techniques. Mad was strongly expressed in differentiating suprab asal keratinocytes in healing dermal wounds and in benign hyperprolife rative conditions, but also in squamous cell carcinomas, in which the keratinocytes retain their differentiation potential. However, Mad exp ression was lost in palisading basal carcinoma cells and poorly differ entiated squamous cell carcinomas, which lacked the epithelial differe ntiation marker syndecan-1. We therefore suggest that Mad expression i s closely associated with epithelial cell differentiation, and that th is association is retained in epithelial tumours of the skin.