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    Impaired cell cycle regulation of the osteoblast-related heterodimeric transcription factor Runx2-Cbfbeta in osteosarcoma cells

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    Authors
    San Martin, Inga A.
    Varela, Nelson
    Gaete, Marcia
    Villegas, Karina
    Osorio, Mariana
    Tapia, Julio
    Antonelli, Marcelo
    Mancilla, Edna E.
    Pereira, Barry P.
    Nathan, Saminathan S.
    Lian, Jane B.
    Stein, Janet L.
    Stein, Gary S.
    Van Wijnen, Andre J.
    Galindo, Mario
    Show allShow less
    UMass Chan Affiliations
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    2009-12-10
    Keywords
    Animals
    Cell Cycle
    Cell Line
    Cell Line, Tumor
    Core Binding Factor Alpha 1 Subunit
    Core Binding Factor beta Subunit
    Cysteine Proteinase Inhibitors
    G1 Phase
    Gene Expression
    Gene Expression Regulation, Neoplastic
    Humans
    Leupeptins
    Mice
    Mitosis
    Osteoblasts
    Osteosarcoma
    Proteasome Endopeptidase Complex
    Rats
    Ubiquitination
    Cell Biology
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    Link to Full Text
    http://dx.doi.org/10.1002/jcp.21894
    Abstract
    Bone formation and osteoblast differentiation require the functional expression of the Runx2/Cbfbeta heterodimeric transcription factor complex. Runx2 is also a suppressor of proliferation in osteoblasts by attenuating cell cycle progression in G(1). Runx2 levels are modulated during the cell cycle, which are maximal in G(1) and minimal beyond the G(1)/S phase transition (S, G(2), and M phases). It is not known whether Cbfbeta gene expression is cell cycle controlled in preosteoblasts nor how Runx2 or Cbfbeta are regulated during the cell cycle in bone cancer cells. We investigated Runx2 and Cbfbeta gene expression during cell cycle progression in MC3T3-E1 osteoblasts, as well as ROS17/2.8 and SaOS-2 osteosarcoma cells. Runx2 protein levels are reduced as expected in MC3T3-E1 cells arrested in late G(1) (by mimosine) or M phase (by nocodazole), but not in cell cycle arrested osteosarcoma cells. Cbfbeta protein levels are cell cycle independent in both osteoblasts and osteosarcoma cells. In synchronized MC3T3-E1 osteoblasts progressing from late G1 or mitosis, Runx2 levels but not Cbfbeta levels are cell cycle regulated. However, both factors are constitutively elevated throughout the cell cycle in osteosarcoma cells. Proteasome inhibition by MG132 stabilizes Runx2 protein levels in late G(1) and S in MC3T3-E1 cells, but not in ROS17/2.8 and SaOS-2 osteosarcoma cells. Thus, proteasomal degradation of Runx2 is deregulated in osteosarcoma cells. We propose that cell cycle control of Runx2 gene expression is impaired in osteosarcomas and that this deregulation may contribute to the pathogenesis of osteosarcoma.
    Source
    J Cell Physiol. 2009 Dec;221(3):560-71. Link to article on publisher's site
    DOI
    10.1002/jcp.21894
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49599
    PubMed ID
    19739101
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/jcp.21894
    Scopus Count
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