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Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma.
Oncogene. 2003 Jan 09; 22(1):1-9.O

Abstract

The chromosomal translocation specifically linked to the Ewing sarcoma family results in the generation of fusion proteins comprising the amino terminal portion of EWS and the DNA-binding domain of ets transcription factors. The EWS/ets chimeric proteins act as aberrant transcription factors leading to tumorigenic processes. We searched for genes specifically activated in Ewing sarcoma cells but not in other tumor cell lines using the gene array technique, and found significantly enhanced expression of the Id2 gene. High levels of Id2 transcripts were detected in Ewing sarcoma cell lines and tumor tissues. The EWS/ets chimeric proteins activated the Id2 gene via the 5'-upstream promoter sequence. Chromatin-immunoprecipitation revealed a direct interaction of EWS/Fli-1 with the promoter regions of the Id2, TGF-beta type II receptor, cyclin D1, and c-myc genes. Since EWS/Fli-1 transactivates c-myc, a cooperative action of the chimeric protein and c-myc leads to overexpression of Id2. In the present study, we suggest that Id2 is a target of the chimeric proteins and that the c-myc/Id2 pathway plays a pivotal role in the tumorigenic processes provoked by EWS/ets proteins.

Authors+Show Affiliations

Department of Pathology, Keio University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12527902

Citation

Fukuma, Mariko, et al. "Upregulation of Id2, an Oncogenic Helix-loop-helix Protein, Is Mediated By the Chimeric EWS/ets Protein in Ewing Sarcoma." Oncogene, vol. 22, no. 1, 2003, pp. 1-9.
Fukuma M, Okita H, Hata J, et al. Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma. Oncogene. 2003;22(1):1-9.
Fukuma, M., Okita, H., Hata, J., & Umezawa, A. (2003). Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma. Oncogene, 22(1), 1-9.
Fukuma M, et al. Upregulation of Id2, an Oncogenic Helix-loop-helix Protein, Is Mediated By the Chimeric EWS/ets Protein in Ewing Sarcoma. Oncogene. 2003 Jan 9;22(1):1-9. PubMed PMID: 12527902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma. AU - Fukuma,Mariko, AU - Okita,Hajime, AU - Hata,Jun-Ichi, AU - Umezawa,Akihiro, PY - 2003/1/16/pubmed PY - 2003/1/31/medline PY - 2003/1/16/entrez SP - 1 EP - 9 JF - Oncogene JO - Oncogene VL - 22 IS - 1 N2 - The chromosomal translocation specifically linked to the Ewing sarcoma family results in the generation of fusion proteins comprising the amino terminal portion of EWS and the DNA-binding domain of ets transcription factors. The EWS/ets chimeric proteins act as aberrant transcription factors leading to tumorigenic processes. We searched for genes specifically activated in Ewing sarcoma cells but not in other tumor cell lines using the gene array technique, and found significantly enhanced expression of the Id2 gene. High levels of Id2 transcripts were detected in Ewing sarcoma cell lines and tumor tissues. The EWS/ets chimeric proteins activated the Id2 gene via the 5'-upstream promoter sequence. Chromatin-immunoprecipitation revealed a direct interaction of EWS/Fli-1 with the promoter regions of the Id2, TGF-beta type II receptor, cyclin D1, and c-myc genes. Since EWS/Fli-1 transactivates c-myc, a cooperative action of the chimeric protein and c-myc leads to overexpression of Id2. In the present study, we suggest that Id2 is a target of the chimeric proteins and that the c-myc/Id2 pathway plays a pivotal role in the tumorigenic processes provoked by EWS/ets proteins. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/12527902/Upregulation_of_Id2_an_oncogenic_helix_loop_helix_protein_is_mediated_by_the_chimeric_EWS/ets_protein_in_Ewing_sarcoma_ DB - PRIME DP - Unbound Medicine ER -