Expression of a smaller lecithin : retinol acyl transferase transcript andreduced retinol esterification in MCF-7 cells

Retinyl ester concentration is regulated by retinoic acid (RA) through an a utoregulatory loop, which acts on lecithin:retinol acyltransferase (LRAT). me tested whether retinol esterification activity is downregulated in human mammary carcinoma cells and whether LRAT expression is RAR-regulated. Norm al human mammary epithelial (HMEC) cells expressed a retinoid-upregulated 5 -kb LRAT transcript and synthesized retinyl esters from H-3-retinol. Human carcinoma MCF-7 cells failed to express the 5-kb LRAT transcript and to syn thesize retinyl esters. Instead, they expressed a 2.7-kb LRAT transcript. B oth transcripts were upregulated by RA. Stable expression of the dominant-n egative RAR alpha 403 blunted the up-regulation of LRAT mRNA by RA, We conc lude that retinol esterification is decreased in MCF-7 vs normal mammary ce lls; that these cancer cells express a shorter (2.7 kb) LRAT transcript, an d that retinoid receptors are involved in the regulation of LRAT-mediated r etinyl ester synthesis by RA. (C) 2000 Academic Press.