Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS-WT1 fusion protein.
Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS-WT1 fusion protein.
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EWS-WT1 融合蛋白的新型亚型对 IGF-I 受体基因表达的转录调节。
DOI：
10.1038/sj.onc.1205042
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Werner,Haim
中科院分区：
文献类型：
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作者：
Finkeltov,Ina;Kuhn,Scott;Glaser,Tova;Idelman,Gila;Wright,JohnJ;RobertsJr,CharlesT;Werner,Haim
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.
