Tags

Type your tag names separated by a space and hit enter

Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells Results in EWS/FLI-1-dependent, ewing sarcoma-like tumors.
Cancer Res. 2005 Oct 01; 65(19):8698-705.CR

Abstract

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

Authors+Show Affiliations

Hamon Center for Therapeutic Oncology Research, Department of Pathology, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16204038

Citation

Castillero-Trejo, Yeny, et al. "Expression of the EWS/FLI-1 Oncogene in Murine Primary Bone-derived Cells Results in EWS/FLI-1-dependent, Ewing Sarcoma-like Tumors." Cancer Research, vol. 65, no. 19, 2005, pp. 8698-705.
Castillero-Trejo Y, Eliazer S, Xiang L, et al. Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells Results in EWS/FLI-1-dependent, ewing sarcoma-like tumors. Cancer Res. 2005;65(19):8698-705.
Castillero-Trejo, Y., Eliazer, S., Xiang, L., Richardson, J. A., & Ilaria, R. L. (2005). Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells Results in EWS/FLI-1-dependent, ewing sarcoma-like tumors. Cancer Research, 65(19), 8698-705.
Castillero-Trejo Y, et al. Expression of the EWS/FLI-1 Oncogene in Murine Primary Bone-derived Cells Results in EWS/FLI-1-dependent, Ewing Sarcoma-like Tumors. Cancer Res. 2005 Oct 1;65(19):8698-705. PubMed PMID: 16204038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells Results in EWS/FLI-1-dependent, ewing sarcoma-like tumors. AU - Castillero-Trejo,Yeny, AU - Eliazer,Susan, AU - Xiang,Lilin, AU - Richardson,James A, AU - Ilaria,Robert L,Jr PY - 2005/10/6/pubmed PY - 2005/12/15/medline PY - 2005/10/6/entrez SP - 8698 EP - 705 JF - Cancer research JO - Cancer Res VL - 65 IS - 19 N2 - Ewing sarcoma is the second most common malignant pediatric bone tumor. Over 80% of Ewing sarcoma contain the oncogene EWS/FLI-1, which encodes the EWS/FLI-1 oncoprotein, a hybrid transcription factor comprised of NH2-terminal sequences from the RNA-binding protein EWS and the DNA-binding and COOH-terminal regions of the Ets transcription factor FLI-1. Although numerous genes are dysregulated by EWS/FLI-1, advances in Ewing sarcoma cancer biology have been hindered by the lack of an animal model because of EWS/FLI-1-mediated cytotoxicity. In this study, we have developed conditions for the isolation and propagation of murine primary bone-derived cells (mPBDC) that stably express EWS/FLI-1. Early-passage EWS/FLI-1 mPBDCs were immortalized in culture but inefficient at tumor induction, whereas later-passage cells formed sarcomatous tumors in immunocompetent syngeneic mice. Murine EWS/FLI-1 tumors contained morphologically primitive cells that lacked definitive lineage markers. Molecular characterization of murine EWS/FLI-1 tumors revealed that some but not all had acquired a novel, clonal in-frame p53 mutation associated with a constitutive loss of p21 expression. Despite indications that secondary events facilitated EWS/FLI-1 mPBDC tumorigenesis, cells remained highly dependent on EWS/FLI-1 for efficient transformation in clonogenic assays. This Ewing sarcoma animal model will be a useful tool for dissecting the molecular pathogenesis of Ewing sarcoma and provides rationale for the broader use of organ-specific progenitor cell populations for the study of human sarcoma. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/16204038/Expression_of_the_EWS/FLI_1_oncogene_in_murine_primary_bone_derived_cells_Results_in_EWS/FLI_1_dependent_ewing_sarcoma_like_tumors_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16204038 DB - PRIME DP - Unbound Medicine ER -