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| IDENTIFICATION OF TARGET GENES FOR THE EWINGS-SARCOMA EWS/FLI FUSION PROTEIN BY REPRESENTATIONAL DIFFERENCE ANALYSIS |
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| Author(s): BRAUN BS, FRIEDEN R, LESSNICK SL, MAY WA, DENNY CT |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 15 Issue: 8 Pages: 4623-4630 Published: AUG 1995 |
| Times Cited: 127 References: 56 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF LOS ANGELES, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA
2. UNIV CALIF LOS ANGELES, SCH MED, JONSSON COMPREHENS CANC CTR, LOS ANGELES, CA 90024 USA
3. UNIV CALIF LOS ANGELES, DEPT PEDIAT, GWYNNE HAZEN CHERRY MEM LABS, DIV HEMATOL ONCOL, LOS ANGELES, CA 90024 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: RJ779 |
| ISSN: 0270-7306 |
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