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

Saminathan S. Nathan, Barry P. Pereira, Ye Fang Zhou, Anurag Gupta, Christian Dombrowski, Ritchie Soong, Robert W H Pho, Gary S. Stein, Manuel Salto-Tellez, Simon M. Cool, Andre J van Wijnen

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)153-158
Number of pages6
JournalMolecular Biology Reports
Volume36
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Osteosarcoma
Osteoblasts
Genomic Instability
Growth
DNA Damage
Transcription Factors
Cell Culture Techniques
Cell Line
Mutation
Proteins

Keywords

  • Human osteosarcoma
  • Osteoblast
  • p53/p21 pathway
  • pRB gene
  • Runx2

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Nathan, S. S., Pereira, B. P., Zhou, Y. F., Gupta, A., Dombrowski, C., Soong, R., ... van Wijnen, A. J. (2009). Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma. Molecular Biology Reports, 36(1), 153-158. https://doi.org/10.1007/s11033-008-9378-1

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

In: Molecular Biology Reports, Vol. 36, No. 1, 01.2009, p. 153-158.

Research output: Contribution to journalArticle

Nathan, SS, Pereira, BP, Zhou, YF, Gupta, A, Dombrowski, C, Soong, R, Pho, RWH, Stein, GS, Salto-Tellez, M, Cool, SM & van Wijnen, AJ 2009, 'Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma', Molecular Biology Reports, vol. 36, no. 1, pp. 153-158. https://doi.org/10.1007/s11033-008-9378-1
Nathan SS, Pereira BP, Zhou YF, Gupta A, Dombrowski C, Soong R et al. Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma. Molecular Biology Reports. 2009 Jan;36(1):153-158. https://doi.org/10.1007/s11033-008-9378-1
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. / Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma. In: Molecular Biology Reports. 2009 ; Vol. 36, No. 1. pp. 153-158.
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