Your browser version may not work well with NCBI's Web applications. More information here...
1: Cancer Res. 2008 Nov 1;68(21):8968-75.
Related Articles, Links
Click here to read Click here to read
EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model.

Lin PP, Pandey MK, Jin F, Xiong S, Deavers M, Parant JM, Lozano G.

Department of Orthopaedic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. plin@mdanderson.org

Ewing's sarcoma is characterized by the t(11;22)(q24:q12) reciprocal translocation. To study the effects of the fusion gene EWS-FLI1 on development and tumor formation, a transgenic mouse model was created. A strategy of conditional expression was used to limit the potentially deleterious effects of EWS-FLI1 to certain tissues. In the absence of Cre recombinase, EWS-FLI1 was not expressed in the EWS-FLI1 transgenic mice, and they had a normal phenotype. When crossed to the Prx1-Cre transgenic mouse, which expresses Cre recombinase in the primitive mesenchymal cells of the embryonic limb bud, the EF mice were noted to have a number of developmental defects of the limbs. These included shortening of the limbs, muscle atrophy, cartilage dysplasia, and immature bone. By itself, EWS-FLI1 did not induce the formation of tumors in the EF transgenic mice. However, in the setting of p53 deletion, EWS-FLI1 accelerated the formation of sarcomas from a median time of 50 to 21 weeks. Furthermore, EWS-FLI1 altered the type of tumor that formed. Conditional deletion of p53 in mesenchymal cells (Prx1-Cre p53(lox/lox)) produced osteosarcomas as the predominant tumor. The presence of EWS-FLI1 shifted the tumor phenotype to a poorly differentiated sarcoma. The results taken together suggest that EWS-FLI1 inhibits normal limb development and accelerates the formation of poorly differentiated sarcomas.

Publication Types:
PMID: 18974141 [PubMed - indexed for MEDLINE]