Submitted May 9, 2007
Accepted October 1, 2007
The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma
Manik Chatterjee*, Christoph Rancso, Thorsten Stuhmer, Niels Eckstein, Mindaugas Andrulis, Christian Gerecke, Heike Lorentz, Hans-Dieter Royer, and Ralf C Bargou
Department of Internal Medicine II, Division of Hematology, University Hospital of Wurzburg, Wurzburg, Germany
Department of Pathology, Helios Clinics, Berlin, Germany
Breast Cancer Research Group, Center for Advanced European Studies and Research (CAESAR), Bonn, Germany
Institute of Pathology, University of Heidelberg, Heidelberg, Germany
Department of Hematology, Oncology and Tumorimmunology, Robert Rossle Cancer Center at the Max Delbruck Center for Molecular Medicine, Berlin, Germany
* Corresponding author; email: chatterjee_m{at}medizin.uni-wuerzburg.de.
Current knowledge about molecular mechanisms underlying disease progression and drug resistance in multiple myeloma (MM) is still limited. Here, we analyzed the potential pathogenetic role of the Y box binding protein YB-1 in MM. YB-1 is a member of the cold shock domain protein superfamily and involved in various cellular functions like proliferation. Immunohistochemical analyses revealed that neither normal bone marrow (BM) plasma cells (PCs), premalignant PCs of patients with monoclonal gammopathy of unknown significance (MGUS) nor MM cells with a mature morphology showed expression of YB-1 in situ. In contrast, YB-1 was strongly expressed in situ in normal PC precursor blasts as well as in a MM subset and in vitro in all of the evaluated MM cell lines. The YB-1 expressing MM cells were characterized by an immature morphology and a highly proliferative phenotype as defined by Ki 67 expression. We observed that siRNA-mediated knockdown of YB-1 decreased proliferation and induced apoptosis in MM cells even in the presence of BM stromal cells. Furthermore, we found that overexpression of YB-1 mediated resistance towards doxorubicin-induced apoptosis in MM cells. Thus, YB-1 contributes to disease progression, survival and drug resistance in MM and might therefore provide an attractive therapeutic target.
