Journal
CANCER CELL
Volume 26, Issue 3, Pages 390-401Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2014.07.023
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Funding
- NIH [AR061565, HD022657, DE016990]
- Cancer Prevention and Research Institute of Texas [RP101017]
- BCM Intellectual and Developmental Disabilities Research Center from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD024064]
- BCM Advanced Technology Cores [AI036211, P30 CA125123, RR024574]
- Cancer Fighters of Houston
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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 the NICD 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.
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