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 3H-labeled phosphatidylethanol in cells prelabeled with [3H]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 wild-type 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.
Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
C J
CJ
Welsh
G C
GC
Yeh
J M
JM
Phang
D001943:Breast Neoplasms / Q000201:enzymology*; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D004351:Drug Resistance; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D009227:Myristic Acids; D010712:Phosphatidic Acids; D019814:Myristic Acid; D004317:Doxorubicin; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate