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 pho spholipase D activity of approximately 4-6 times over that found in wi ld type cells. Phospholipase D activity was assessed by monitoring the mass of phorbol ester-induced phosphatidylethanol. The cellular phosp holipase D activity was time- and phorbol ester-concentration-dependen t and was obvious whether measured as an increase in the mass of PEt o r in the production of H-3-labeled phosphatidylethanol in cells prelab eled with [H-3]myristic acid. Phorbol ester also stimulated increases in the production of the mass of cellular diacylglycerol and phosphati dic acid in the adriamycin-resistant cells vs. the wildtype cells. Tes ts with a series of drug-resistant MCF-7 cell lines revealed a positiv e correlation between increased drug resistance and phorbol ester-stim ulated phospholipase D activity. (C) 1994 Academic Press, Inc.