Document Detail

Multifunctional role of Erk5 in multiple myeloma.
MedLine Citation:
PMID:  15692064     Owner:  NLM     Status:  MEDLINE    
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.
Xonia Carvajal-Vergara; Soraya Tabera; Juan C Montero; Azucena Esparís-Ogando; Ricardo López-Pérez; Gema Mateo; Norma Gutiérrez; Marisa Parmo-Cabañas; Joaquín Teixidó; Jesús F San Miguel; Atanasio Pandiella
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-02-03
Journal Detail:
Title:  Blood     Volume:  105     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-20     Completed Date:  2005-07-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4492-9     Citation Subset:  AIM; IM    
Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Spain.
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MeSH Terms
Antineoplastic Agents / pharmacology
Boronic Acids / pharmacology
Cell Proliferation
Dexamethasone / pharmacology
Enzyme Activation / drug effects
Interleukin-6 / pharmacology
Mitogen-Activated Protein Kinase 7 / analysis,  physiology*
Multiple Myeloma / enzymology*,  etiology,  pathology
Pyrazines / pharmacology
Signal Transduction
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Boronic Acids; 0/Interleukin-6; 0/Pyrazines; 0/bortezomib; 50-02-2/Dexamethasone; EC Protein Kinase 7

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