IMPLICATION OF RETINOIC ACID RECEPTOR-GAMMA IN SQUAMOUS DIFFERENTIATION AND RESPONSE TO RETINOIC ACID IN HEAD AND NECK SQCC Y1 SQUAMOUS CARCINOMA-CELLS/

Nuclear retinoic acid receptors are considered to be the mediators of most of the effects of retinoic acid (RA) on gene expression. To explo re the role of RA receptor gamma (RAR gamma) in the growth and differe ntiation of SqCC/Y1 head and neck squamous carcinoma cells, they were transfected with RAR gamma sense and antisense expression vectors and stable clones in which RAR gamma expression was either increased or bl ocked were isolated. The growth inhibitory effect of RA in monolayer c ulture was enhanced in the sense transfectants and decreased in the an tisense ones. The ability to form colonies in semisolid medium was abo lished by RA in the sense transfectants, while the antisense transfect ed clones exhibited heterogeneous responses. The expression of the squ amous differentiation markers cytokeratin K1, transglutaminase type I, and involucrin was increased in the absence of exogenous retinoid in a sense transfected clone and decreased in an antisense transfected cl one. RA suppressed squamous differentiation in both types of transfect ant. The expression of epidermal growth factor receptor (EGFR) was hig her in the antisense and lower in the sense transfectant than in the p arental cells and RA decreased EGFR mRNA level in the parental and the sense transfectant but not in the antisense transfectant. In addition activator protein-1 (AP-1) binding activity was decreased by the RA t reatment in the sense clones, but not in the antisense ones. These res ults suggest that RAR gamma mediates the effects of RA on the cell gro wth both in monolayer culture and in semisolid medium possibly through AP-1 suppression.