Expression of a smaller lecithin:retinol acyl transferase transcript and reduced retinol esterification in MCF-7 cells.
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.
Andreola
F
F
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Giandomenico
V
V
Spero
R
R
De Luca
L M
LM
D000217:Acyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D004951:Esterification; D006801:Humans; D008970:Molecular Weight; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000502:physiology; D012176:Retinoids / Q000494:pharmacology; D014158:Transcription, Genetic; D014316:Tritium; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D014801:Vitamin A / Q000378:metabolism*
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014316:Tritium; D014801:Vitamin A; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase