Retinyl Methyl Ether: Binding to Transport Proteins and Effect on Transcriptional Regulation

• Published in: Biochemical and biophysical research communications 1996-06, Vol.223 (2), p.293-298
• Main Authors: Sani, Brahma P., Zhang, Xiao-kun, Hill, Donald L., Shealy, Y.Fulmer
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - metabolism; Anticarcinogenic Agents - pharmacology; Cell Line; Cell Nucleus - metabolism; Chlorocebus aethiops; Female; Macromolecular Substances; Mammary Neoplasms, Experimental - prevention & control; Protein Multimerization; Rats; Receptors, Retinoic Acid - drug effects; Receptors, Retinoic Acid - metabolism; Recombinant Proteins - metabolism; Retinoic Acid Receptor alpha; Retinoic Acid Receptor gamma; Retinoid X Receptors; Retinol-Binding Proteins - drug effects; Retinol-Binding Proteins - metabolism; Retinol-Binding Proteins, Cellular; Transcription Factors - drug effects; Transcription Factors - metabolism; Transcription, Genetic - drug effects; Transfection; Vitamin A - analogs & derivatives; Vitamin A - metabolism; Vitamin A - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.0887

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 10−9–10−6M, RME did not activate transcription by either of the heterodimers (RARα,β,or γ/RXRα) or the homodimer (RARα/RARα). The retinoid, however, exhibited concentration-dependent inhibitory effects on the basal level of transcriptional activity (no other retinoid added) of both the RARβ- and RARγ/RXRα heterodimers and of the retinoic acid-induced transcriptional activation of the RARγ/RXRα receptors. Thus, RME acted as a retinoic acid antagonist, a role possibly involved in its cancer preventive activity.