The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines

Claudia M.J. Lucero, Oscar A. Vega, Mariana M. Osorio, Julio C. Tapia, Marcelo Antonelli, Gary S. Stein, Andre J. van Wijnen, Mario A. Galindo

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Runx2 regulates osteogenic differentiation and bone formation, but also suppresses pre-osteoblast proliferation by affecting cell cycle progression in the G1 phase. The growth suppressive potential of Runx2 is normally inactivated in part by protein destabilization, which permits cell cycle progression beyond the G1/S phase transition, and Runx2 is again up-regulated after mitosis. Runx2 expression also correlates with metastasis and poor chemotherapy response in osteosarcoma. Here we show that six human osteosarcoma cell lines (SaOS, MG63, U2OS, HOS, G292, and 143B) have different growth rates, which is consistent with differences in the lengths of the cell cycle. Runx2 protein levels are cell cycle-regulated with respect to the G1/S phase transition in U2OS, HOS, G292, and 143B cells. In contrast, Runx2 protein levels are constitutively expressed during the cell cycle in SaOS and MG63 cells. Forced expression of Runx2 suppresses growth in all cell lines indicating that accumulation of Runx2 in excess of its pre-established levels in a given cell type triggers one or more anti-proliferative pathways in osteosarcoma cells. Thus, regulatory mechanisms controlling Runx2 expression in osteosarcoma cells must balance Runx2 protein levels to promote its putative oncogenic functions, while avoiding suppression of bone tumor growth.

Original languageEnglish (US)
Pages (from-to)714-723
Number of pages10
JournalJournal of Cellular Physiology
Volume228
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines'. Together they form a unique fingerprint.

  • Cite this

    Lucero, C. M. J., Vega, O. A., Osorio, M. M., Tapia, J. C., Antonelli, M., Stein, G. S., van Wijnen, A. J., & Galindo, M. A. (2013). The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines. Journal of Cellular Physiology, 228(4), 714-723. https://doi.org/10.1002/jcp.24218