Title | Notch activation as a driver of osteogenic sarcoma. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Tao, J, Jiang, M-M, Jiang, L, Salvo, JS, Zeng, H-C, Dawson, B, Bertin, TK, Rao, PH, Chen, R, Donehower, LA, Gannon, F, Lee, BH |
Journal | Cancer Cell |
Volume | 26 |
Issue | 3 |
Pagination | 390-401 |
Date Published | 2014 Sep 08 |
ISSN | 1878-3686 |
Keywords | Animals, Bone Neoplasms, Carcinogenesis, Cell Line, Tumor, Humans, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Neoplasm Transplantation, Osteoblasts, Osteosarcoma, Protein Structure, Tertiary, Receptor, Notch1, Transcriptome |
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 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. |
DOI | 10.1016/j.ccr.2014.07.023 |
Alternate Journal | Cancer Cell |
PubMed ID | 25203324 |
PubMed Central ID | PMC4159617 |
Grant List | R01 DE016990 / DE / NIDCR NIH HHS / United States HD022657 / HD / NICHD NIH HHS / United States AI036211 / AI / NIAID NIH HHS / United States U54 HD083092 / HD / NICHD NIH HHS / United States DE016990 / DE / NIDCR NIH HHS / United States R03 AR061565 / AR / NIAMS NIH HHS / United States P30 HD024064 / HD / NICHD NIH HHS / United States P30 CA125123 / CA / NCI NIH HHS / United States AR061565 / AR / NIAMS NIH HHS / United States T32 EY007102 / EY / NEI NIH HHS / United States HD024064 / HD / NICHD NIH HHS / United States P01 HD022657 / HD / NICHD NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States P01 HD070394 / HD / NICHD NIH HHS / United States RR024574 / RR / NCRR NIH HHS / United States |
Notch activation as a driver of osteogenic sarcoma.
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