FUNCTIONAL CONSEQUENCES OF REDUCED RETINOIC ACID RECEPTOR-GAMMA EXPRESSION IN A HUMAN SQUAMOUS-CELL CARCINOMA LINE

Nuclear receptors for retinoic acid are important modulators of epider mal cell proliferation and terminal differentiation. Aberrant expressi on of retinoic acid receptors (RARs) and retinoid x receptors in the e pidermis has been associated with altered differentiation capacity and tumor progression. In this study, we describe a human squamous cell c arcinoma line, SCC 12F, which displays reduced RAR gamma expression an d diminished responsiveness to retinoic acid. When compared with norma l keratinocytes or other squamous cell carcinoma lines that display no rmal levels of RAR gamma, several measures of cellular response to ret inoic acid are altered in SCC 12F cells, including inhibition of corni fied envelope formation, reduction of involucrin mRNA expression, and transcriptional regulation of the involucrin gene. Normal patterns of ligand-dependent transcriptional response were restored upon co-transf ection of an expression vector containing either RAR alpha or RAR gamm a. Our findings demonstrate that reduced expression of RAR may have di rect functional consequences with regard to keratinocyte differentiati on and that the defect may be alleviated by reintroduction of function al receptor.