Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines.
When exogenous [(3)H]retinol (vitamin A) was added to culture medium, normal human epithelial cells from the oral cavity, skin, lung and breast took up and esterified essentially all of the [(3)H]retinol within a few hours. As shown by [(3)H]retinol pulse-chase experiments, normal epithelial cells then slowly hydrolyzed the [(3)H]retinyl esters to [(3)H]retinol, some of which was then oxidized to [(3)H]retinoic acid (RA) over a period of several days. In contrast, cultured normal human fibroblasts and human umbilical vein endothelial cells (HUVEC) did not esterify significant amounts of [(3)H]retinol; this lack of [(3)H]retinol esterification was correlated with a lack of expression of lecithin:retinol acyltransferase (LRAT) transcripts in normal fibroblast and HUVEC strains. These results indicate that normal, differentiated cell types differ in their ability to esterify retinol. Human carcinoma cells (neoplastically transformed epithelial cells) of the oral cavity, skin and breast did not esterify much [(3)H]retinol and showed greatly reduced LRAT expression. Transcripts of the neutral, bile salt-independent retinyl ester hydrolase and the bile salt-dependent retinyl ester hydrolase were undetectable in all of the normal cell types, including the epithelial cells. These experiments suggest that retinoid-deficiency in the tumor cells could develop because of the lack of retinyl esters, a storage form of retinol.
Guo
X
X
Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Ruiz
A
A
Rando
R R
RR
Bok
D
D
Gudas
L J
LJ
D000217:Acyltransferases / Q000096:biosynthesis* / Q000235:genetics; D001940:Breast / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism*; D004952:Esters / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009055:Mouth / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000378:metabolism* / Q000493:pharmacokinetics
D004952:Esters; D014316:Tritium; D014801:Vitamin A; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase