title: Multifunctional role of Erk5 in multiple myeloma.
abstract: Multiple myeloma is characterized by the accumulation of terminally differentiated B cells in the bone marrow, due to increased proliferation and restricted apoptosis of the myelomatous clone. Here we have studied the participation of a novel mitogen-activated protein kinase (MAPK) route, the extracellular signal-regulated kinase 5 (Erk5) pathway, in the regulation of myeloma cell proliferation and apoptosis. Erk5 was expressed in cells isolated from patients and in myeloma cell lines. The myeloma growth factor interleukin 6 (IL-6) activated Erk5, and this activation was independent of Ras and Src. Expression of a dominant-negative form of Erk5 restricted the proliferation of myeloma cells and inhibited IL-6-dependent cell duplication. This dominant-negative form also sensitized myeloma cells to the proapoptotic action of dexamethasone and PS341. The latter compound caused a profound decrease in the amount of endogenous Erk5 and was less effective in inducing apoptosis when the level of Erk5 was increased by transfection of Erk5. These results place the Erk5 route as a new regulatory signaling pathway that affects multiple myeloma proliferation and apoptosis.
authors.affiliation: Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Spain.
authors.forename: Xonia
authors.initials: X
authors.lastname: Carvajal-Vergara
authors.forename: Soraya
authors.initials: S
authors.lastname: Tabera
authors.forename: Juan C
authors.initials: JC
authors.lastname: Montero
authors.forename: Azucena
authors.initials: A
authors.lastname: Esparís-Ogando
authors.forename: Ricardo
authors.initials: R
authors.lastname: López-Pérez
authors.forename: Gema
authors.initials: G
authors.lastname: Mateo
authors.forename: Norma
authors.initials: N
authors.lastname: Gutiérrez
authors.forename: Marisa
authors.initials: M
authors.lastname: Parmo-Cabañas
authors.forename: Joaquín
authors.initials: J
authors.lastname: Teixidó
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D048054:Mitogen-Activated Protein Kinase 7 / Q000032:analysis / Q000502:physiology*; D009101:Multiple Myeloma / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D015850:Interleukin-6; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D048054:Mitogen-Activated Protein Kinase 7