This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eliazer, S.
Right arrow Articles by Ilaria, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eliazer, S.
Right arrow Articles by Ilaria, R. L., Jr.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2003, p. 482-492, Vol. 23, No. 2
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.2.482-492.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Alteration of Mesodermal Cell Differentiation by EWS/FLI-1, the Oncogene Implicated in Ewing's Sarcoma

Susan Eliazer,1 Jeffrey Spencer,2 Dan Ye,1 Eric Olson,2 and Robert L. Ilaria Jr.1*

Division of Hematology-Oncology, Department of Medicine, Simmons Cancer Center and Hamon Center for Therapeutic Oncology Research,1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas2

Received 13 May 2002/ Returned for modification 17 July 2002/ Accepted 15 October 2002

The chimeric fusion gene EWS/FLI-1 is detected in most cases of Ewing's sarcoma (ES), the second most common malignant bone tumor of childhood. Although 80% of ES tumors develop in skeletal sites, the remainder can arise in almost any soft tissue location. The lineage of the cell developing the EWS/FLI-1 gene fusion has not been fully characterized but is generally considered to be of either mesenchymal or neural crest origin. To study this oncogene in a conceptually relevant target cell, EWS/FLI-1 was introduced into the murine cell line C2C12, a myoblast cell line capable of differentiation into muscle, bone, or fat. In this cellular context, EWS/FLI-1 profoundly inhibited the myogenic differentiation program. The block in C2C12 myogenic differentiation required the nuclear localization and DNA-binding functions of EWS/FLI-1 and was mediated by transcriptional and posttranscriptional suppression of the myogenic transcription factors MyoD and myogenin. Interestingly, C2C12-EWS/FLI-1 cells constitutively expressed alkaline phosphatase, a bone lineage marker, and were alkaline phosphatase positive by histochemistry but showed no other evidence of bone lineage commitment. Consistent with recent findings in human ES tumor cell lines, C2C12-EWS/FLI-1 cells constitutively expressed cyclin D1 and demonstrated decreased expression of the cell cycle regulator p21cip1, even under differentiation conditions and at confluent density. This C2C12-EWS/FLI-1 cell model may assist in the identification of novel differentially expressed genes relevant to ES and provide further insight into the cell(s) of origin developing ES-associated genetic fusions.

* Corresponding author. Mailing address: Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., MC 8593, Dallas, TX 75390-8593. Phone: (214) 648-1632. Fax: (214) 648-4940. E-mail: Robert.Ilaria{at}utsouthwestern.edu.

Molecular and Cellular Biology, January 2003, p. 482-492, Vol. 23, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.2.482-492.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lin, P. P., Pandey, M. K., Jin, F., Xiong, S., Deavers, M., Parant, J. M., Lozano, G. (2008). EWS-FLI1 Induces Developmental Abnormalities and Accelerates Sarcoma Formation in a Transgenic Mouse Model. Cancer Res. 68: 8968-8975 [Abstract] [Full Text]  
  • Liu, S., Cheng, H., Kwan, W., Lubieniecka, J. M., Nielsen, T. O. (2008). Histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in clear cell sarcoma models. Molecular Cancer Therapeutics 7: 1751-1761 [Abstract] [Full Text]  
  • Luan, Y., Yu, X.-P., Yang, N., Frenkel, S., Chen, L., Liu, C.-j. (2008). p204 Protein Overcomes the Inhibition of Core Binding Factor {alpha}-1-mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins. Mol. Biol. Cell 19: 2113-2126 [Abstract] [Full Text]  
  • Riggi, N., Suva, M.-L., Suva, D., Cironi, L., Provero, P., Tercier, S., Joseph, J.-M., Stehle, J.-C., Baumer, K., Kindler, V., Stamenkovic, I. (2008). EWS-FLI-1 Expression Triggers a Ewing's Sarcoma Initiation Program in Primary Human Mesenchymal Stem Cells. Cancer Res. 68: 2176-2185 [Abstract] [Full Text]  
  • Miyagawa, Y., Okita, H., Nakaijima, H., Horiuchi, Y., Sato, B., Taguchi, T., Toyoda, M., Katagiri, Y. U., Fujimoto, J., Hata, J.-i., Umezawa, A., Kiyokawa, N. (2008). Inducible Expression of Chimeric EWS/ETS Proteins Confers Ewing's Family Tumor-Like Phenotypes to Human Mesenchymal Progenitor Cells. Mol. Cell. Biol. 28: 2125-2137 [Abstract] [Full Text]  
  • Luan, Y., Yu, X.-P., Xu, K., Ding, B., Yu, J., Huang, Y., Yang, N., Lengyel, P., Di Cesare, P. E., Liu, C.-j. (2007). The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity. J. Biol. Chem. 282: 16860-16870 [Abstract] [Full Text]  
  • El-Deiry, W. S., Sigman, C. C., Kelloff, G. J. (2006). Imaging and Oncologic Drug Development. JCO 24: 3261-3273 [Abstract] [Full Text]  
  • Ye, D., Wolff, N., Li, L., Zhang, S., Ilaria, R. L. Jr (2006). STAT5 signaling is required for the efficient induction and maintenance of CML in mice. Blood 107: 4917-4925 [Abstract] [Full Text]  
  • Castillero-Trejo, Y., Eliazer, S., Xiang, L., Richardson, J. A., Ilaria, R. L. Jr. (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 Res. 65: 8698-8705 [Abstract] [Full Text]  
  • Nozawa, S., Ohno, T., Banno, Y., Dohjima, T., Wakahara, K., Fan, D.-G., Shimizu, K. (2005). Inhibition of Platelet-derived Growth Factor-induced Cell Growth Signaling by a Short Interfering RNA for EWS-Fli1 via Down-regulation of Phospholipase D2 in Ewing Sarcoma Cells. J. Biol. Chem. 280: 27544-27551 [Abstract] [Full Text]  
  • Hu-Lieskovan, S., Zhang, J., Wu, L., Shimada, H., Schofield, D. E., Triche, T. J. (2005). EWS-FLI1 Fusion Protein Up-regulates Critical Genes in Neural Crest Development and Is Responsible for the Observed Phenotype of Ewing's Family of Tumors. Cancer Res. 65: 4633-4644 [Abstract] [Full Text]  
  • Liu, C.-j., Chang, E., Yu, J., Carlson, C. S., Prazak, L., Yu, X.-P., Ding, B., Lengyel, P., Cesare, P. E. D. (2005). The Interferon-inducible p204 Protein Acts as a Transcriptional Coactivator of Cbfa1 and Enhances Osteoblast Differentiation. J. Biol. Chem. 280: 2788-2796 [Abstract] [Full Text]  
  • Zhang, J., Hu, S., Schofield, D. E., Sorensen, P. H. B., Triche, T. J. (2004). Selective Usage of D-Type Cyclins by Ewing's Tumors and Rhabdomyosarcomas. Cancer Res. 64: 6026-6034 [Abstract] [Full Text]  
  • Torchia, E. C., Jaishankar, S., Baker, S. J. (2003). Ewing Tumor Fusion Proteins Block the Differentiation of Pluripotent Marrow Stromal Cells. Cancer Res. 63: 3464-3468 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»