DERMAL FIBROBLASTS TUMOR SUPPRESSION OF RAS-TRANSFORMED KERATINOCYTESIS ASSOCIATED WITH INDUCTION OF SQUAMOUS-CELL DIFFERENTIATION

We have previously reported that tumor formation of ras-transformed ke ratinocytes can be suppressed by dermal fibroblasts through production of a diffusible growth inhibitory factor of the transforming growth f actor-beta (TGF-beta) family. Keratinocytes transformed by ras and E1a oncogenes or papilloma-derived keratinocytes transformed by a ras onc ogene show concomitant resistance to dermal fibroblast tumor suppressi on and TGF-beta growth inhibition We report here that dermal fibroblas t tumor suppression is associated with a striking induction of squamou s cell differentiation and that this effect is blocked in tumors resis tant to dermal fibroblast inhibition. This experimental system strongl y supports the notion that suppression of tumorigenicity and induction of a differentiated phenotype are closely associated events.