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Mol. Cell. Biol., 08 1995, 4623-4630, Vol 15, No. 8
BS Braun, R Frieden, SL Lessnick, WA May and CT Denny
The EWS/FLI-1 fusion gene results from the 11;22 chromosomal translocation
in Ewing's sarcoma. The product of the gene is one of a growing number of
structurally altered transcription factors implicated in oncogenesis. We
have employed a subtractive cloning strategy of representational difference
analysis in conjunction with a model transformation system to identify
genes transcribed in response to EWS/FLI. We have characterized eight
transcripts that are dependent on EWS/FLI for expression and two
transcripts that are repressed in response to EWS/FLI. Three of the former
were identified by sequence analysis as stromelysin 1, a murine homolog of
cytochrome P-450 F1 and cytokeratin 15. Stromelysin 1 is induced rapidly
after expression of EWS/FLI, suggesting that the stromelysin 1 gene may be
a direct target gene of EWS/FLI. These results demonstrate that expression
of EWS/FLI leads to significant changes in the transcription of specific
genes and that these effects are at least partially distinct from those
caused by expression of germ line FLI-1. The representational difference
analysis technique can potentially be applied to investigate transformation
pathways activated by a broad array of genes in different tumor systems.
Copyright © 1995, American Society for Microbiology
Identification of target genes for the Ewing's sarcoma EWS/FLI fusion protein by representational difference analysis
Molecular Biology Institute, University of California, Los Angeles 90024, USA.
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