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| THE EWINGS-SARCOMA EWS/FLI-1 FUSION GENE ENCODES A MORE POTENT TRANSCRIPTIONAL ACTIVATOR AND IS A MORE POWERFUL TRANSFORMING GENE THAN FLI-1 |
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| Author(s): MAY WA, LESSNICK SL, BRAUN BS, KLEMSZ M, LEWIS BC, LUNSFORD LB, HROMAS R, DENNY CT |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 13 Issue: 12 Pages: 7393-7398 Published: DEC 1993 |
| Times Cited: 282 References: 33 |
| Abstract: EWS/FLI-1 is a chimeric protein formed by a tumor-specific 11;22 translocation found in both Ewing's sarcoma and primitive neuroectodermal tumor of childhood. EWS/FLI-1 has been shown to be a potent transforming gene, suggesting that it plays an important role in the genesis of these human tumors. We now demonstrate that EWS/FLI-1 has the characteristics of an aberrant transcription factor. Subcellular fractionation experiments localized the EWS/FLI-1 protein to the nucleus of primitive neuroectodermal tumor cells. EWS/FLI-1 specifically bound in vitro an ets-2 consensus sequence similarly to normal FLI-1. When coupled to a GAL4 DNA-binding domain, the amino-terminal EWS/FLI-1 region was a much more potent transcriptional activator than the corresponding amino-terminal domain of FLI-1. Finally, EWS/FLI-1 efficiently transformed NIH 3T3 cells, but FLI-1 did not. These data suggest that EWS/FLI-1, functioning as a transcription factor, leads to a phenotype dramatically different from that of cells expressing FLI-1. EWS/FLI-1 could disrupt normal growth and differentiation either by more efficiently activating FLI-1 target genes or by inappropriately modulating genes normally not responsive to FLI-1. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF LOS ANGELES, DEPT PEDIAT, DIV HEMATOL ONCOL, GWYNNE HAZEN CHERRY MEM LABS, 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, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA
4. INDIANA UNIV, MED CTR, DEPT MICROBIOL & IMMUNOL, INDIANAPOLIS, IN 46202 USA
5. INDIANA UNIV, MED CTR, DIV HEMATOL ONCOL, INDIANAPOLIS, IN 46202 USA
6. INDIANA UNIV, MED CTR, WALTHER ONCOL CTR, INDIANAPOLIS, IN 46202 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: MJ341 |
| ISSN: 0270-7306 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |