Transcriptional activation of a model reporter system by retinoids and retinoic acid receptor isoforms.
Retinoic acid (RA) and its congeners mediate their biologic effects after binding to nuclear transcription factors called retinoic acid receptors. Biological effects and binding affinities to various receptors vary widely. Activation of transcription ability for selected retinoids was investigated using a standardized model system. CV-1 cells were cotransfected with a retinoic acid responsive reporter plasmid and expression vectors for retinoic acid receptors (RARs, alpha, beta or gamma) and/or retinoic X receptor (RXR alpha), and were treated with a retinoid (all-trans-RA, 13-cis-RA, Ro 12-4894, SRI 5898-21, or Ro 13-7410). Gene transcription for all retinoids tested was activated in a dose-dependent manner. All-trans-RA was the most potent activator of RAR alpha while SRI 5898-21 was the least active. RAR alpha and RAR beta showed similar levels of activation with all the retinoids tested, Ro 12-4894 and Ro 13-7410 induced little transcription in the presence of RAR gamma. Cotransfection of RXR alpha with the RARs changed the ability of the retinoids to activate transcription. Transcriptional activation in cells cotransfected with RXR and RAR beta or RAR gamma was lower than in cells cotransfected with RAR beta alone or RAR gamma alone. Such models with specific responsive elements may be useful for evaluating the relative activity of various retinoids in vitro, however, complex interactions are likely depending on the choice of the reporter construct and other transcription factors available in the cell.
Huggenvik
J I
JI
Center for Environmental Toxicology, Utah State University, Logan 84322-5600, USA.
Sharma
R P
RP
D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D010957:Plasmids; D018168:Receptors, Retinoic Acid / Q000187:drug effects*; D012176:Retinoids / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D015500:Chloramphenicol O-Acetyltransferase