Tamoxifen stimulates phospholipase D activity by an estrogen receptor-independent mechanism.
The effects of tamoxifen (TAM), a widely used agent in the treatment of breast cancer, were examined on phospholipase D (PLD)-mediated phospholipid hydrolysis. In drug-sensitive MCF-7 human breast carcinoma cells TAM, similar to several well-established activators of PLD, had no effect on phospholipid hydrolysis. In an estrogen receptor-deficient multidrug-resistant subline of MCF-7 cells, TAM preferentially stimulated the hydrolysis of phosphatidylethanolamine; two-fold stimulation required 2.5 or 5 microM TAM in the absence or presence of serum, respectively. In NIH 3T3 fibroblasts significant (4- to 4.8-fold) stimulation of phosphatidylethanolamine and phosphatidylcholine hydrolysis in the presence of serum required 10 microM TAM. These data establish that TAM can stimulate PLD activity by an estrogen receptor-independent mechanism.
Kiss
Z
Z
Hormel Institute, University of Minnesota, Austin 55912.
D016475:3T3 Cells; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011960:Receptors, Estrogen; D013629:Tamoxifen; D010739:Phospholipase D