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Expression of a smaller lecithin:retinol acyl transferase transcript and reduced retinol esterification in MCF-7
F Andreola1, V Giandomenico, R Spero
1Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Abstract:
Retinyl ester concentration is regulated by retinoic acid (RA) through an autoregulatory loop, which acts on lecithin:retinol acyltransferase (LRAT). We tested whether retinol esterification activity is downregulated in human mammary carcinoma cells and whether LRAT expression is RAR-regulated. Normal human mammary epithelial (HMEC) cells expressed a retinoid-upregulated 5-kb LRAT transcript and synthesized retinyl esters from 3H-retinol. Human carcinoma MCF-7 cells failed to express the 5-kb LRAT transcript and to synthesize retinyl esters. Instead, they expressed a 2.7-kb LRAT transcript. Both transcripts were upregulated by RA. Stable expression of the dominant-negative RARalpha403 blunted the up-regulation of LRAT mRNA by RA. We conclude that retinol esterification is decreased in MCF-7 vs normal mammary cells; that these cancer cells express a shorter (2.7 kb) LRAT transcript, and that retinoid receptors are involved in the regulation of LRAT-mediated retinyl ester synthesis by RA.