ACCUMULATION OF FATTY ALCOHOL IN MCF-7 BREAST-CANCER CELLS

The MCF-7 cell line (human breast epithelial cells) accumulates fatty alcohols. The fatty alcohols were identified as C16:0, C18:0, and C18: 1 alcohols by thin-layer chromatography and gas chromatography/mass sp ectrometry. This accumulation of alcohols in MCF-7 was found in cultur es of MCF-7 cells obtained from other laboratories but not in a variet y of unrelated cell lines. The presence of the alcohols suggested an a berrant ether lipid metabolism in the MCF-7 cells. Therefore, the capa city for ether lipid biosynthesis was evaluated using cells incubated with either [C-14]stearyl alcohol or [C-14]stearic acid. MCF-7 cells i ncorporated less than 0.4% of the [C-14]alcohol into ether-linked phos pholipids, whereas the AB589 breast epithelial cells, used as a ''norm al control'' for comparisons, did not accumulate fatty alcohol and inc orporated approximately 20% of the radiolabeled alcohol into phospholi pids containing ether linkages. Although the MCF-7 cells were unable t o effectively incorporate the fatty alcohol into ether linkages, the c ells were able to oxidize the alcohol to fatty acid. When incubated wi th [C-14]stearic acid, the conversion to radiolabeled fatty alcohol in MCF-7 cells was approximately four times higher than the alcohol leve ls found in AB589 cells. While deficient in the ability to synthesize ether linkages, the MCF-7 cells did incorporate radiolabeled hexadecyl glycerol, a precursor containing an ether linkage, into phospholipids. Collectively, the data indicate that the MCF-7 cells possess a defici ency in the alkyl DHAP synthase activity. A near absence of ether-link ed lipids in the MCF-7 cells was indicated by the radiolabeling studie s, and this finding was corroborated by results from HPLC analysis. An alyses of the partial glycerides, obtained from the enzymatic hydrolys is of cellular phospholipids, found only trace levels of ether lipids in the MCF-7 cells. The aberration in ether lipid biosynthesis did not correlate with the expression of the multidrug resistance phenotype i n a series multidrug resistant MCF-7 variants. The results are discuss ed relative to the use of the MCF-7 cells as a model for investigation s of ether lipid biosynthesis and the cellular physiology of ether lip ids. (C) 1994 Academic Press, Inc.