Notch Activation as a Driver of Osteogenic Sarcoma

Jianning Tao, Ming Ming Jiang, Lichun Jiang, Jason S. Salvo, Huan Chang Zeng, Brian Dawson, Terry K. Bertin, Pulivarthi H. Rao, Rui Chen, Lawrence A. Donehower, Francis Gannon, Brendan H. Lee

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Osteogenic sarcoma (OS) is a deadly skeletal malignancy whose cause is unknown. We report here a mouse model of OS based on conditional expression of the intracellular domain of Notch1 (NICD). Expression of theNICD in immature osteoblasts was sufficient to drive the formation of bone tumors, including OS, with complete penetrance. These tumors display features of human OS; namely, histopathology, cytogenetic complexity, and metastatic potential. We show that Notch activation combined with loss of p53 synergistically accelerates OS development in mice, although p53-driven OS is not Rbpj dependent, which demonstrates a dual dominance of the Notch oncogene and p53 mutation in the development of OS. Using this model, we also reveal the osteoblasts as the potential sources of OS.

Original languageEnglish (US)
Pages (from-to)390-401
Number of pages12
JournalCancer Cell
Volume26
Issue number3
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Tao, J., Jiang, M. M., Jiang, L., Salvo, J. S., Zeng, H. C., Dawson, B., Bertin, T. K., Rao, P. H., Chen, R., Donehower, L. A., Gannon, F., & Lee, B. H. (2014). Notch Activation as a Driver of Osteogenic Sarcoma. Cancer Cell, 26(3), 390-401. https://doi.org/10.1016/j.ccr.2014.07.023