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Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7129-33.

A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects.

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  • 1Pharma Division, Preclinical Research, F. Hoffmann-La Roche, Basel, Switzerland.


Retinoic acid (RA) exerts its pleiotropic effects on cell growth and differentiation through the activation of a family of transcription factors-the RA receptors (RARs). Three subtypes of these receptors exist, RAR alpha, RAR beta, and RAR gamma. The receptors are differentially expressed in different cell types and stages of development, suggesting that they may regulate different sets of genes. We have identified a synthetic retinoid with the characteristics of a selective RAR alpha antagonist. This antagonist counteracts RA effects on HL-60 cell differentiation and on B-lymphocyte polyclonal activation. Beyond its potential practical relevance, this and other specific antagonists will be useful to dissect the RAR system and to assign to one given receptor each of the many RA-regulated functions.

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