RETINOID REGULATION OF HUMAN ECTOCERVICAL EPITHELIAL-CELL TRANSGLUTAMINASE ACTIVITY AND KERATIN GENE-EXPRESSION

Cornified envelope formation, the level of transglutaminase activity a nd the pattern of cytokeratin gene expression are important biochemica l markers of cervical epithelial cell differentiation in vivo. In the present study we examine the effects of retinoid treatment on transglu taminase (TG) activity and keratin gene expression in cultured human e ctocervical epithelial cells (ECE cells). All-trans-retinoic acid (RA) and a synthetic retinoid, Ro 13-6298, suppress TG activity by 85-90% with half-maximal inhibition at 0.1 nM Ro 13-6298 or 1 nM RA. In contr ast, the predominant circulating retinoid, retinol, does not inhibit T G activity. The level of type I transglutaminase protein, measured usi ng a type I TG-specific antibody, decreases in parallel with the decre ase in activity as does the level of the TG RNA transcript. Cytokerati n K16 decreases more than 20-fold while the level of K7, K8 and K19 in crease 5 to 10-fold in the presence of 10 nM RA. Studies using cDNAs e ncoding K5, K13, K16 and K19 indicate that the RNA transcript levels c hange in parallel with the change in keratin protein production. Thus, all-trans-retinoic acid suppresses ectocervical epithelial cell diffe rentiation in vitro, a result that suggests an in vivo role for retino ids in regulating cervical cell differentiation.