title: Inhibition of phorbol ester-stimulated phospholipase D activity by chronic tamoxifen treatment in breast cancer cells.
abstract: We have shown that in an estrogen receptor-negative multidrug-resistant subline of MCF-7 human breast carcinoma cells longer-term (24 h), but not shorter-term (30 min), treatments with clinically relevant (2-5 microM) concentrations of tamoxifen (TAM) inhibited phorbol ester-stimulated phospholipase D (PLD) activity by 50-80%. TAM caused these inhibitory effects without inducing membrane translocation or down-regulation of protein kinase C-alpha, the major mediator of phorbol ester effects on PLD activation. The results raise the possibility that prolonged inhibition of the protein kinase C-alpha-regulated PLD system may contribute to the cytotoxic effects of tamoxifen in estrogen receptor-negative breast cancer cells.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. kissx001@maroon.tc.umn.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Kiss
authors.forename: W H
authors.initials: WH
authors.lastname: Anderson
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen; D011493:Protein Kinase C; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate