Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS-WT1 fusion protein
- 13 March 2002
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 21 (12), 1890-1898
- https://doi.org/10.1038/sj.onc.1205042
Abstract
The EWS family of genes is involved in numerous chromosomal translocations that are characteristic of a variety of sarcomas. A recently described member of this group is desmoplastic small round cell tumor (DSRCT), which is characterized by a recurrent t(11;22)(p13;q12) translocation that fuses the 5' exons of the EWS gene to the 3' exons of the WT1 gene. The originally described chimera comprises exons 1-7 of EWS and exons 8-10 of WT1. We have previously reported that the WT1 protein represses the expression of the IGF-I receptor gene, whereas the EWS(1-7)-WT1(8-10) fusion protein activates IGF-I receptor gene expression. It has recently become apparent that EWS-WT1 chimeras produced in DSCRT are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We have recently characterized additional EWS-WT1 translocations that involve the juxtaposition of EWS exons 7 or 8 to WT1 exon 8, and an EWS-WT1 chimera that lacks EWS exon 6. The chimeric transcription factors encoded by these various translocations differ in their DNA-binding characteristics and their ability to transactivate the IGF-I receptor promoter. These data suggest that the molecular pathology of DSRCT is more complex than previously appreciated, and that this diversity may provide the foundation for predictive genotype-phenotype correlations in the future.Keywords
This publication has 34 references indexed in Scilit:
- Tumor Cell Viability in Clear Cell Sarcoma Requires DNA Binding Activity of the EWS/ATF1 Fusion ProteinPublished by Elsevier BV ,1999
- Variant EWS-WT1 Chimeric Product in the Desmoplastic Small Round Cell TumorPediatric and Developmental Pathology, 1999
- Molecular Variants of the EWS-WT1 Gene Fusion in Desmoplastic Small Round Cell TumorDiagnostic Molecular Pathology, 1998
- EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomenHuman Pathology, 1995
- Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.Proceedings of the National Academy of Sciences, 1995
- The role of the IGF‐I receptor in the growth and transformation of mammalian cellsCell Proliferation, 1994
- The Insulin-Like Growth FactorsAnnual Review of Physiology, 1993
- Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumoursNature, 1992
- Intra-abdominal Desmoplastic Small Round-Cell TumorThe American Journal of Surgical Pathology, 1991
- Intraabdominal Desmoplastic Small-Cell Tumors with Divergent DifferentiationThe American Journal of Surgical Pathology, 1990