Transient Ca2+-dependent activation of ERK1 and ERK2 in cytotoxic responses induced by maitotoxin in breast cancer cells.
Treatment of MCF-7 breast cancer cells with the marine toxin maitotoxin (MTX) induces cell death. The cytotoxic effects are clearly detectable within 2-4 h after cell treatment with 10(-10)-10(-9) M concentrations of MTX. The response was found to depend on extracellular Ca2+, inasmuch as cell death was prevented when culture dishes received MTX, following addition of EGTA. MTX caused transient phosphorylation of extracellular signal-regulated kinase isoforms 1 and 2 (ERK1 and ERK2) mitogen-activated protein kinase isoforms in MCF-7 cells, which was maximal 15 min after toxin addition to culture vessels. The effect was dependent on influx of extracellular Ca2+, as it was abolished by EGTA, and was induced by ionophores, such as A23187 and ionomycin. Our findings show that signaling pathways involving Ca2+ ions may cause activation of ERK1 and ERK2 in cell death responses.
Malaguti
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Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Italy.
Yasumoto
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Paolo Rossini
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D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008387:Marine Toxins / Q000633:toxicity*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D035964:Oxocins; D010766:Phosphorylation / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D000095702:Polyether Toxins
D002118:Calcium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004533:Egtazic Acid; D008387:Marine Toxins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D035964:Oxocins; C020394:maitotoxin; D000095702:Polyether Toxins