INCREASED PHOSPHOLIPASE-D ACTIVITY IN MULTIDRUG-RESISTANT BREAST-CANCER CELLS

An adriamycin-resistant MCF-7 cell line (300-fold increased resistance vs. wild type MCF-7) showed an increased phorbol ester-stimulated phospholipase D activity of approximately 4-6 times over that found in wild type cells. Phospholipase D activity was assessed by monitoring the mass of phorbol ester-induced phosphatidylethanol. The cellular phospholipase D activity was time- and phorbol ester-concentration-dependent and was obvious whether measured as an increase in the mass of PEt or in the production of H-3-labeled phosphatidylethanol in cells prelabeled with [H-3]myristic acid. Phorbol ester also stimulated increases in the production of the mass of cellular diacylglycerol and phosphatidic acid in the adriamycin-resistant cells vs. the wildtype cells. Tests with a series of drug-resistant MCF-7 cell lines revealed a positive correlation between increased drug resistance and phorbol ester-stimulated phospholipase D activity. (C) 1994 Academic Press, Inc.