Retinoic acid upregulates cone arrestin expression in retinoblastoma cells through a Cis element in the distal promoter region.

摘要: PURPOSE This study was initiated to investigate the molecular mechanisms of activation expression human cone arrestin (hCAR) gene by retinoic acid (RA), in an vitro model retinoblastoma cells. METHODS Human Weri-Rb-1 or Y79 cell lines were cultured absence presence RA analogues with transcription translation inhibitors for various periods. The mRNAs encoding hCAR, receptor (RAR), and retinoid X (RXR) subtypes analyzed Northern blot. Immunoblot analysis hCAR protein also performed. promoter's activity its responsiveness treatment evaluated transient transfection promotor-luciferase reporter constructs, followed promoter deletion map specific regions responsible response. RESULTS In our model, both all-trans 9-cis induced mRNA a time- dose-dependent manner. RA's effect blocked either RNA synthesis inhibitors; however, mRNA's stability not affected RA, as determined decay experiments. Although all RAR RXR detected, only RXRgamma RARalpha increased dramatically after RA. An RXR-specific agonist, but RAR-specific stimulated promoter-luciferase studies. Subsequently, region between -852 -702 promoter, RA-responsive elements (RAREs), discovered be CONCLUSIONS is transcriptionally upregulated acting through cis within 5' flanking region. Based on cumulative data, most likely subtype involved regulation