Retinyl methyl ether: binding to transport proteins and effect on transcriptional regulation.
Retinyl methyl ether (RME) which prevents cancers of the rat mammary gland, binds to cellular retinol-binding protein and serum retinol-binding protein but not to cellular retinoic acid-binding protein or to the nuclear retinoid receptors, RARs/RXRs. Since the biochemical effects of retinoids likely involve activation or suppression of RAR/RXR-mediated gene transcription, we evaluated such activity of RME by performing cotransfection assays involving CV-1 cells, expression vectors containing RAR and/or RXR cDNA, and an appropriate reporter vector. In the concentration range of 10(-9)-10(-6), RME did not activate transcription by either of the heterodimers (RARalpha, beta or gamma/RXR alpha) or the homodimer (RARalpha/RARalpha). The retinoid, however, exhibited concentration-dependent inhibitory effects on the basal level of transcriptional activity (no other retinoid added) of both the RAR beta- and RARgamma/RXRalpha heterodimers and of the retinoic acid-induced transcriptional activation of the RARgamma/RXRalpha receptors. Thus, RME acted as a retinoic acid antagonist, a role possibly involved in its cancer preventive activity.
Sani
B P
BP
Southern Research Institute, Birmingham, Alabama 35255-5305, USA.
Zhang
X
X
Hill
D L
DL
Shealy
Y F
YF
D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D005260:Female; D046911:Macromolecular Substances; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control; D055503:Protein Multimerization; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000097768:Retinoic Acid Receptor gamma
D016588:Anticarcinogenic Agents; D046911:Macromolecular Substances; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors; D014801:Vitamin A; D000097768:Retinoic Acid Receptor gamma; C000607073:Rara protein, rat; C082925:retinoic acid receptor beta; C022613:retinyl methyl ether