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A link between basic fibroblast growth factor (bFGF) and EWS/FLI-1 in Ewing's sarcoma cells

Oncogene volume 19, pages 4298–4301 (2000)Cite this article

Abstract

The EWS/FLI-1 fusion gene is characteristic of most cases of Ewing's sarcoma and has been shown to be crucial for tumor transformation and cell growth. In this study we demonstrate a drastic down-regulation of the EWS/FLI-1 protein, and a growth arrest, following serum depletion of Ewing's sarcoma cells. This indicates that growth factor circuits may be involved in regulation of the fusion gene product. Of four different growth factors tested, basic fibroblast growth factor (bFGF) was found to be of particular significance. In fact, upon treatment of serum-depleted cells with bFGF, expression of the EWS/FLI-1 protein and growth of the Ewing's sarcoma cells were restored. In addition, a bFGF-neutralizing antibody, which was confirmed to inhibit FGF receptor (FGFR) phosphorylation, caused down-regulation of EWS/FLI-1. Experiments using specific cell cycle blockers (thymidine and colcemide) suggest that EWS/FLI-1 is directly linked to bFGF stimulation, and not indirectly to cell proliferation. We also demonstrated expression of FGFRs in several tumor samples of Ewing's sarcoma. Taken together, our data suggest that expression of FGFR is a common feature of Ewing's sarcoma and, in particular, that the bFGF pathway may be important for the maintenance of a malignant phenotype of Ewing's sarcoma cells through up-regulating the EWS/FLI-1 protein.

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Acknowledgements

The project was supported by grants from the Swedish Cancer Society, the Cancer Society in Stockholm, and the Karolinska Institute.

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Authors and Affiliations

  1. Department of Oncology and Pathology, Cellular and Molecular Tumor Pathology, CCK, R8:04, Karolinska Hospital, Stockholm, SE-171 76, Sweden

    Leonard Girnita, Ada Girnita, Min Wang & Olle Larsson

  2. Department of Pathology, Musculoskeletal Tumor Center, Sahlgrenska University Hospital, Gothenburg, Sweden

    Jeanne M Meis-Kindblom & Lars-Gunnar Kindblom

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  1. Leonard Girnita
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Girnita, L., Girnita, A., Wang, M. et al. A link between basic fibroblast growth factor (bFGF) and EWS/FLI-1 in Ewing's sarcoma cells. Oncogene 19, 4298–4301 (2000). https://doi.org/10.1038/sj.onc.1203755

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