VARIABLE EXPRESSION OF RETINOIC ACID RECEPTOR (RAR-BETA) MESSENGER-RNA IN HUMAN ORAL AND EPIDERMAL-KERATINOCYTES - RELATION TO KERATIN-19 EXPRESSION AND KERATINIZATION POTENTIAL

Previous studies have revealed that the cells that form the different regions of the oral and epidermal stratified squamous epithelia represent a number of intrinsically distinct keratinocyte subtypes, each of which is developmentally programmed to preferentially express a particular pattern of keratins and type of suprabasal histology. Retinoic acid (RA) is known to modulate stratified squamous epithelial differentiation, including expression of the basal cell keratin K19 and the suprabasal keratins K1/K10 and K4/K13. We have found that all keratinocyte subtypes are similar in their steady state levels of RAR-alpha and RAR-gamma mRNAs in culture and that these levels are only minimally affected by RA. In contrast, RAR-beta mRNA expression varies greatly among keratinocyte subtypes and, in eight of ten cell strains examined, directly correlated with their levels of K19 mRNA. Exposure to 10(-6) M RA increases the levels of RAR-beta and K19 mRNA; conversely, complete removal of RA from the medium results in reduced levels of these messages. RA does not coordinately induce RAR-beta and K19 messages in nonkeratinocyte cell types: fibroblasts cultured in the presence of 10(-6) M RA express very high levels of RAR-beta mRNA but do not express detectable K19, and mesothelial cells decrease their levels of RAR-beta and K19 mRNA in response to 10(-6) M RA. The correlation between RAR-beta and K19 mRNA levels in most keratinocyte subtypes suggests a role for RAR-beta in specifying patterns of keratin expression and suprabasal differentiation in stratified squamous epithelia.