title: Cross-talks between c-Kit and PKC isoforms in HMC-1(560) and HMC-1(560,816) cells. Different role of PKCδ in each cellular line.
abstract: The c-kit inhibitor STI571 represents one of the most important treatments for patients with mastocytosis. However, intracellular pathways modulated by this compound are not completely defined. Here, STI571 effect on Protein Kinase C (PKC) regulation is determined in HMC-1 mast cell lines. STI571 activates PKCδ isoform resulting in HMC-1(560) apoptosis. The apoptosis observed is PKCδ-dependent, since PKCδ-silencing avoids STI571 effect. c-kit inhibition implies nuclear PKCδ translocation characterized by a clear dependence on actin cytoskeleton integrity in HMC-1(560) cell line, but not in HMC-1(560,816). Therefore, PKCδ modulations can lead to a serious decrease in STI571 treatment-effectiveness.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Araceli
authors.initials: A
authors.lastname: Tobío
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Alfonso
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain. Electronic address: Luis.Botana@usc.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001549:Benzamides / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D007527:Isoenzymes; D008407:Mast Cells / Q000276:immunology*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000032:analysis / Q000276:immunology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001549:Benzamides; D007527:Isoenzymes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D011493:Protein Kinase C
keywords: HMC-1; PKC; PMA; STI571; c-kit