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    Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma

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    Authors
    Nathan, Saminathan S.
    Pereira, Barry P.
    Zhou, Ye-fang
    Gupta, Anurag
    Dombrowski, Christian
    Soong, Ritchie
    Pho, Robert W. H.
    Stein, Gary S.
    Salto-Tellez, Manuel
    Cool, Simon M.
    Van Wijnen, Andre J.
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    UMass Chan Affiliations
    Department of Cell Biology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2008-10-22
    Keywords
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://dx.doi.org/10.1007/s11033-008-9378-1
    Abstract
    To understand the molecular etiology of osteosarcoma, we isolated and characterized a human osteosarcoma cell line (OS1). OS1 cells have high osteogenic potential in differentiation induction media. Molecular analysis reveals OS1 cells express the pocket protein pRB and the runt-related transcription factor Runx2. Strikingly, Runx2 is expressed at higher levels in OS1 cells than in human fetal osteoblasts. Both pRB and Runx2 have growth suppressive potential in osteoblasts and are key factors controlling competency for osteoblast differentiation. The high levels of Runx2 clearly suggest osteosarcomas may form from committed osteoblasts that have bypassed growth restrictions normally imposed by Runx2. Interestingly, OS1 cells do not exhibit p53 expression and thus lack a functional p53/p21 DNA damage response pathway as has been observed for other osteosarcoma cell types. Absence of this pathway predicts genomic instability and/or vulnerability to secondary mutations that may counteract the anti-proliferative activity of Runx2 that is normally observed in osteoblasts. We conclude OS1 cells provide a valuable cell culture model to examine molecular events that are responsible for the pathologic conversion of phenotypically normal osteoblast precursors into osteosarcoma cells.
    Source
    Mol Biol Rep. 2009 Jan;36(1):153-8. Epub 2008 Oct 18. Link to article on publisher's site
    DOI
    10.1007/s11033-008-9378-1
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32850
    PubMed ID
    18931939
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1007/s11033-008-9378-1
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    Morningside GSBS Scholarly Publications

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