Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells Results in EWS/FLI-1-dependent, ewing sarcoma-like tumors.

摘要: Ewing sarcoma is the second most common malignant pediatric bone tumor. Over 80% of contain oncogene EWS/FLI-1, which encodes EWS/FLI-1 oncoprotein, a hybrid transcription factor comprised NH2-terminal sequences from RNA-binding protein EWS and DNA-binding COOH-terminal regions Ets FLI-1. Although numerous genes are dysregulated by advances in cancer biology have been hindered lack an animal model because EWS/FLI-1-mediated cytotoxicity. In this study, we developed conditions for isolation propagation murine primary bone-derived cells (mPBDC) that stably express EWS/FLI-1. Early-passage mPBDCs were immortalized culture but inefficient at tumor induction, whereas later-passage formed sarcomatous tumors immunocompetent syngeneic mice. Murine contained morphologically primitive lacked definitive lineage markers. Molecular characterization revealed some not all had acquired novel, clonal in-frame p53 mutation associated with constitutive loss p21 expression. Despite indications secondary events facilitated mPBDC tumorigenesis, remained highly dependent on efficient transformation clonogenic assays. This will be useful tool dissecting molecular pathogenesis provides rationale broader use organ-specific progenitor cell populations study human sarcoma.