title: Retinoic acid and synthetic analogs differentially activate retinoic acid receptor dependent transcription.
abstract: We have developed an assay where the potency of retinoids in retinoic acid receptor (RAR) mediated transcriptional activation can be rapidly evaluated. In this assay hRAR-alpha, hRAR-beta and hRAR-gamma were expressed in CV-1 cells together with a reporter gene containing a retinoic acid responsive element (TRE3-tk-CAT). Concentrations required to obtain half-maximum induction (ED50) of CAT-activity were determined for several retinoids, e.g., all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), arotinoid acid (TTNPB) and m-carboxy-arotinoid acid (m-carboxy-TTNPB, an inactive arotinoid analog). The ED50 values for RA decreased in the order of RAR-alpha (24 nM) greater than RAR-beta (4.0 nM) greater than RAR-gamma (1.3 nM), while the ED50 values for TTNPB and 13-cis-RA decreased in the order of RAR-alpha (6.5 nM, 190 nM) greater than RAR-gamma (2.3 nM, 140 nM) greater than RAR-beta (0.6 nM, 43 nM), respectively. No significant inductions were obtained when cells were treated with m-carboxy-TTNPB, even at 10 microM concentrations. The fold induction of CAT-activity for all compounds tested decreased in the order of RAR-alpha greater than RAR-beta greater than RAR-gamma.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor 48109.
authors.forename: A
authors.initials: A
authors.lastname: Aström
authors.forename: U
authors.initials: U
authors.lastname: Pettersson
authors.forename: A
authors.initials: A
authors.lastname: Krust
authors.forename: P
authors.initials: P
authors.lastname: Chambon
authors.forename: J J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D018168:Receptors, Retinoic Acid; D015183:Restriction Mapping; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D015345:Oligonucleotide Probes; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D015500:Chloramphenicol O-Acetyltransferase