Transcriptional regulation of IGF-I receptor gene expression by the PAX3–FKHR oncoprotein
Copyright policy )Transcriptional regulation of IGF-I receptor gene expression by the PAX3–FKHR oncoprotein
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.
- Tel Aviv University Israel
Osteosarcoma, Chromosomes, Human, Pair 13, Forkhead Box Protein O1, Recombinant Fusion Proteins, Genetic Vectors, Chromosome Mapping, Forkhead Transcription Factors, Soft Tissue Neoplasms, Recombinant Proteins, Receptor, IGF Type 1, DNA-Binding Proteins, Gene Expression Regulation, Chromosomes, Human, Pair 2, Protein Biosynthesis, Rhabdomyosarcoma, Humans, Paired Box Transcription Factors, Child, PAX3 Transcription Factor, Plasmids
Osteosarcoma, Chromosomes, Human, Pair 13, Forkhead Box Protein O1, Recombinant Fusion Proteins, Genetic Vectors, Chromosome Mapping, Forkhead Transcription Factors, Soft Tissue Neoplasms, Recombinant Proteins, Receptor, IGF Type 1, DNA-Binding Proteins, Gene Expression Regulation, Chromosomes, Human, Pair 2, Protein Biosynthesis, Rhabdomyosarcoma, Humans, Paired Box Transcription Factors, Child, PAX3 Transcription Factor, Plasmids
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