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IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells

Luisa Cironi1, Nicolò Riggi, Paolo Provero

  • 1Division of Experimental Pathology, Institute of Pathology CHUV, University of Lausanne, Lausanne, Switzerland.

Plos One
|July 24, 2008
PubMed
Abstract

Insights

Ewing

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ewing's sarcoma family tumors (ESFT) are primarily driven by EWS-FLI-1 fusion proteins, with other chimeric genes implicated in a minority of cases.
  • ESFT growth and survival are critically dependent on insulin-like growth factor-1 (IGF-1).
  • Mesenchymal progenitor/stem cells are a potential cell of origin for ESFT.

Purpose of the Study:

  • To investigate the functional relationships among different ESFT-associated fusion proteins.
  • To compare the ability of mouse progenitor cells (MPCs) to express various ESFT fusion proteins.
  • To analyze the gene expression changes induced by these fusion proteins and identify common mechanisms in ESFT pathogenesis.

Main Methods:

  • Assessed mouse progenitor cell (MPC) permissiveness for expressing EWS-FLI-1, EWS-ERG, and FUS-ERG fusion proteins.
  • Analyzed gene expression profile changes in MPCs following expression of the fusion proteins.
  • Investigated the activation of the IGF1 promoter and IGF1 expression by the fusion proteins.

Main Results:

  • MPC isolates showed variable permissiveness for expressing EWS-FLI-1, EWS-ERG, and FUS-ERG.
  • Transcriptome changes induced by the fusion proteins exhibited limited overlap.
  • All three ESFT fusion proteins, but not FLI-1 or ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression.

Conclusions:

  • Different ESFT-associated fusion proteins may require distinct cellular environments and induce unique transcriptome alterations.
  • IGF1 induction represents a potential common mechanism by which these fusion proteins contribute to ESFT development.
  • Understanding these mechanisms can inform targeted therapeutic strategies for ESFT.

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