Sry. Cajal et al., DERMAL FIBROBLASTS TUMOR SUPPRESSION OF RAS-TRANSFORMED KERATINOCYTESIS ASSOCIATED WITH INDUCTION OF SQUAMOUS-CELL DIFFERENTIATION, The American journal of pathology, 145(4), 1994, pp. 846-855
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.