Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation.
-
- W A May
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- M L Gishizky
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- S L Lessnick
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- L B Lunsford
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- B C Lewis
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- O Delattre
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- J Zucman
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- G Thomas
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
-
- C T Denny
- Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles 90024.
抄録
<jats:p>The 11;22 chromosomal translocation specifically linked to Ewing sarcoma and primitive neuroectodermal tumor results in a chimeric molecule fusing the amino-terminal-encoding portion of the EWS gene to the carboxyl-terminal DNA-binding domain encoded by the FLI1 gene. We have isolated a fourth EWS-FLI1 fusion cDNA that is structurally distinct from the three forms previously described. To determine the transforming activity of this gene, alternative forms of the EWS-FLI1 fusion were transduced into NIH 3T3 cells. Cells expressing either type 1 or type 4 fusion constructs formed foci in culture and colonies in soft agar, indicating that EWS-FLI1 is a transforming gene. EWS-FLI1 deletion mutants were created to map functionally the critical regions within the chimera. Deletion of either the EWS domain or the FLI1 corresponding to the DNA-binding domain totally abrogated the ability for EWS-FLI1 to transform 3T3 cells. These data indicate that the oncogenic effect of the 11;22 translocation is caused by the formation of a chimeric transcription factor. Formation of chimeric transcription factors has now been demonstrated to promote tumors of both neuroectodermal and hematopoietic origin, suggesting that this may be a common mechanism in human carcinogenesis.</jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 90 (12), 5752-5756, 1993-06-15
Proceedings of the National Academy of Sciences
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1361137043634010880
-
- NII論文ID
- 30016294214
-
- ISSN
- 10916490
- 00278424
-
- データソース種別
-
- Crossref
- CiNii Articles