Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein

Growth Horm IGF Res. 2001 Oct;11(5):289-97. doi: 10.1054/ghir.2001.0244.


Chromosomal translocations that disrupt the molecular organization of transcription factors are typical of a variety of solid and hematopoietic cancers. Alveolar rhabdomyosarcoma (ARMS), a paediatric soft tissue malignant tumour, is characterized by the recurrent translocation t(2;13)(q35;q14) that fuses the 5' DNA binding domain-encoding sequences of the Pax3 gene with the 3' sequences of the FKHR gene. The insulin-like growth factor (IGF) system has an important role in muscle development as well as in the aetiology of paediatric sarcomas, including ARMS. In the present study the potential regulation of the IGF-I receptor (IGF-I-R) gene by PAX3-FKHR at the transcriptional level was investigated. PAX3-FKHR was able to transactivate the IGF-I-R promoter in sarcoma-derived cell lines, whereas PAX3 exhibited a reduced potency in comparison to the fusion protein. Furthermore, transfection of the chimera induced a significant increase in the endogenous levels of IGF-I-R protein, suggesting that the IGF-I-R gene is a physiologically-relevant molecular target for the PAX3-FKHR oncogene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 13
  • Chromosomes, Human, Pair 2
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Gene Expression Regulation*
  • Genetic Vectors
  • Humans
  • Osteosarcoma / genetics
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Plasmids
  • Protein Biosynthesis
  • Receptor, IGF Type 1 / genetics*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Rhabdomyosarcoma / genetics
  • Soft Tissue Neoplasms / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection
  • Translocation, Genetic
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Pax3 protein, mouse
  • Receptor, IGF Type 1