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Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts.
Oncogene. 1995 Sep 21; 11(6):1049-54.O

Abstract

Cytogenetic analysis of Ewing's sarcoma, primitive neuroectodermal tumors and Askin tumors revealed characteristic translocations t(11;22) or t(21;22). Molecular analysis of these translocations revealed 5'-region of EWS gene (from band 22q12) is fused to the 3'-region of either Fli-1 gene (from band 11q24) or erg gene (from band 21q22). Functional characterization of the EWS-Fli-1 and EWS-erg chimeric proteins suggested that they function as transcriptional activators. In order to develop therapeutic agents, it is essential to know whether expression of the EWS-fusion gene products is coupled to tumorigenicity of Ewing's sarcoma cells and if targeting the EWS-fusion products results in loss of tumorigenicity of Ewing's sarcoma cells. For this reason, we have made stable Ewing's sarcomas expressing antisense EWS-Fli-1 or EWS-erg expression plasmids. Expression of antisense EWS fusion transcripts resulted in a significant loss of endogenous EWS-Fli-1 and EWS-erg proteins in Ewing's sarcoma cells. These cells expressing antisense EWS fusion transcripts showed loss of anchorage independent growth and tumorigenicity in nude mice unlike the parental Ewing's sarcoma cells. These results demonstrate the necessity of a certain threshold level of expression of EWS-fusion products in the clonogenicity and tumorigenicity of Ewing's sarcoma cells and therefore emphasizes the importance of targeting the EWS-fusion products as a therapy for Ewing family of tumors.

Authors+Show Affiliations

Department of Microbiology and Immunology, Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107-5541, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7566963

Citation

Ouchida, M, et al. "Loss of Tumorigenicity of Ewing's Sarcoma Cells Expressing Antisense RNA to EWS-fusion Transcripts." Oncogene, vol. 11, no. 6, 1995, pp. 1049-54.
Ouchida M, Ohno T, Fujimura Y, et al. Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene. 1995;11(6):1049-54.
Ouchida, M., Ohno, T., Fujimura, Y., Rao, V. N., & Reddy, E. S. (1995). Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene, 11(6), 1049-54.
Ouchida M, et al. Loss of Tumorigenicity of Ewing's Sarcoma Cells Expressing Antisense RNA to EWS-fusion Transcripts. Oncogene. 1995 Sep 21;11(6):1049-54. PubMed PMID: 7566963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. AU - Ouchida,M, AU - Ohno,T, AU - Fujimura,Y, AU - Rao,V N, AU - Reddy,E S, PY - 1995/9/21/pubmed PY - 1995/9/21/medline PY - 1995/9/21/entrez SP - 1049 EP - 54 JF - Oncogene JO - Oncogene VL - 11 IS - 6 N2 - Cytogenetic analysis of Ewing's sarcoma, primitive neuroectodermal tumors and Askin tumors revealed characteristic translocations t(11;22) or t(21;22). Molecular analysis of these translocations revealed 5'-region of EWS gene (from band 22q12) is fused to the 3'-region of either Fli-1 gene (from band 11q24) or erg gene (from band 21q22). Functional characterization of the EWS-Fli-1 and EWS-erg chimeric proteins suggested that they function as transcriptional activators. In order to develop therapeutic agents, it is essential to know whether expression of the EWS-fusion gene products is coupled to tumorigenicity of Ewing's sarcoma cells and if targeting the EWS-fusion products results in loss of tumorigenicity of Ewing's sarcoma cells. For this reason, we have made stable Ewing's sarcomas expressing antisense EWS-Fli-1 or EWS-erg expression plasmids. Expression of antisense EWS fusion transcripts resulted in a significant loss of endogenous EWS-Fli-1 and EWS-erg proteins in Ewing's sarcoma cells. These cells expressing antisense EWS fusion transcripts showed loss of anchorage independent growth and tumorigenicity in nude mice unlike the parental Ewing's sarcoma cells. These results demonstrate the necessity of a certain threshold level of expression of EWS-fusion products in the clonogenicity and tumorigenicity of Ewing's sarcoma cells and therefore emphasizes the importance of targeting the EWS-fusion products as a therapy for Ewing family of tumors. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/7566963/Loss_of_tumorigenicity_of_Ewing's_sarcoma_cells_expressing_antisense_RNA_to_EWS_fusion_transcripts_ L2 - https://www.lens.org/lens/search/patent/list?q=citation_id:7566963 DB - PRIME DP - Unbound Medicine ER -