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The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma

Item Type:Article
Title:The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma
Creators Name:Chatterjee, M. and Rancso, C. and Stuehmer, T. and Eckstein, N. and Andrulis, M. and Gerecke, C. and Lorentz, H. and Royer, H.D. and Bargou, R.C.
Abstract: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 such as 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 toward 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.
Keywords:Antineoplastic Antibiotics, Apoptosis, Bone Marrow, Tumor Cell Line, Cell Proliferation, DNA-Binding Proteins, Doxorubicin, Neoplasm Drug Resistance, Neoplastic Gene Expression Regulation, Immunohistochemistry, Ki-67 Antigen, Lymphoid Progenitor Cells, Multiple Myeloma, Nuclear Proteins, Plasma Cells, Small Interfering RNA, Stromal Cells
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:111
Number:7
Page Range:3714-3722
Date:1 April 2008
Official Publication:https://doi.org/10.1182/blood-2007-05-089151
PubMed:View item in PubMed

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