@article{feaad37b5b924ea8b49f86b8ef9ea40f,
title = "Notch Activation as a Driver of Osteogenic Sarcoma",
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.",
author = "Jianning Tao and Jiang, {Ming Ming} and Lichun Jiang and Salvo, {Jason S.} and Zeng, {Huan Chang} and Brian Dawson and Bertin, {Terry K.} and Rao, {Pulivarthi H.} and Rui Chen and Donehower, {Lawrence A.} and Francis Gannon and Lee, {Brendan H.}",
note = "Funding Information: We thank C. Lietman, S. Chen, Y. Bae, P. Campeau, L. Wang, J. Yustein, K. Scott, L. Kurenbekova, and members of the B.H.L. lab for technical assistance and/or discussions. We thank P. Fonseca for editorial assistance. This work was supported by the NIH (AR061565 to J.T.; HD022657 and DE016990 to B.H.L.) and the Cancer Prevention and Research Institute of Texas (RP101017 to B.H.L.). This work was also supported by the BCM Intellectual and Developmental Disabilities Research Center (grant HD024064 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development), the BCM Advanced Technology Cores (AI036211, P30 CA125123, and RR024574), and Cancer Fighters of Houston. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
doi = "10.1016/j.ccr.2014.07.023",
language = "English (US)",
volume = "26",
pages = "390--401",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}