Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma
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.
Document Type
Journal ArticlePublication Date
2008-10-22
Metadata
Show full item recordAbstract
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 siteDOI
10.1007/s11033-008-9378-1Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32850PubMed ID
18931939Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1007/s11033-008-9378-1