SPECIFICITY OF RETINOID RECEPTOR GENE-EXPRESSION IN MOUSE CERVICAL EPITHELIA

Retinoids are powerful regulators of epithelial differentiation and ar e essential for its maintenance. Because retinoids are necessary for c ervical epithelial differentiation, they have been used as chemopreven tive agents of cervical dysplasia and neoplasia. We were interested in determining whether different cervical epithelial phenotypes express specific retinoid receptors. The cervical epithelium contains the two phenotypes, stratified squamous and simple columnar, which join at the squamocolumnar junction. In addition, the simple columnar epithelium undergoes squamous metaplasia in response to vitamin A deficiency. The refore, the cervical epithelium is suitable to study the expression pa ttern of the retinoid receptors in the three phenotypes, simple column ar, stratified squamous, and squamous metaplastic, simultaneously. The distribution pattern of the major retinoic acid receptor (RAR) isofor ms (alpha 1, alpha 2, beta 2, beta 3, gamma 1, and gamma 2) and retino id-X receptors (RXR alpha, -beta, and -gamma) was studied by in situ h ybridization. At the tissue level, RAR alpha (1 and 2) and RXR (alpha and beta) transcripts and, to a lesser extent, RAR gamma (1 and 2) tra nscripts were associated with the cervical stratified squamous subjunc tional epithelium. The simple columnar epithelium, which is highly res ponsive to vitamin A status, expressed high levels of RAR alpha (1 and 2), RAR beta (2 and 3), and RXR (alpha and beta) transcripts. Only RA R beta (2 and 3) and RXR (alpha and beta) transcripts were downmodulat ed by the condition of vitamin A deficiency and expressed less in squa mous metaplastic foci than the simple columnar epithelium. RXR gamma w as undetectable in all three cervical epithelia. At the cellular level , basal and suprabasal expression was found for RARs, and preferential localization of RXRs was seen in basal cells. RXRs are auxiliary prot eins for a variety of other nuclear receptors with which they form het erodimers, including RARs. The fact that RXRs are mainly localized in basal and columnar cells of the cervix suggests the need for the regul ation and diversity generated by potential heterodimeric interactions in these rapidly proliferating cells in vivo. The unique pattern of ex pression and localization of the RARs and RXRs in different cervical e pithelial tissues and cell types supports the hypothesis that they per form specific functions in cervical epithelial differentiation. This i s in contrast to the major isoforms of each RAR, which have similar pa tterns of expression in the different cervical epithelial phenotypes a nd cell types, suggesting a redundancy in function.