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Article: Transformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1

TitleTransformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1
Authors
KeywordsEwing's sarcoma
EWS
Fli-1
KRAB
Represser
Issue Date2003
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal Of Cancer, 2003, v. 88 n. 1, p. 137-145 How to Cite?
AbstractEwing's sarcoma is a childhood bone tumour with poor prognosis, most commonly associated with a t(11;22)(q24;q12) reciprocal translocation that fuses the EWS and FLI-1 genes, resulting in the production of an aberrant chimeric transcription factor EWS/FLI-1. To erucidate the mechanisms by which EWS/FLI-1 mediates transformation in mouse models, we have generated a murine Ews/Fli-1 fusion protein. We demonstrate that this protein transforms fibroblast celrs in vitro similar to human EWS/FLI-1 as demonstrated by serum and anchorage-independent growth, the formation of tumours in nude mice and elevation of the oncogenic marker c-myc. Furthermore, transformation of these cells was inhibited by a specific represser, KRAB/FLI-1. The KRAB/FLI-1 repressor also suppressed the tumorigenic phenotype of a human Ewing's sarcoma cell line. These findings suggest that the transformed phenotype of Ewing's sarcoma cells can be reversed by using the sequence-specific FLI-1-DNA-binding domain to target a gone repressor domain. The inhibition of EWS/FLI-1 is the first demonstration of the KRAB domain suppressing the action of an ETS factor. This approach provides potential avenues for the elucidation of the biological mechanisms of EWS/FLI-1 oncogenesis and the development of novel therapeutic strategies. © 2003 Cancer Research UK.
Persistent Identifierhttp://hdl.handle.net/10722/88695
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, Den_HK
dc.contributor.authorWilson, TJen_HK
dc.contributor.authorXu, Den_HK
dc.contributor.authorCowdery, HEen_HK
dc.contributor.authorSanij, Een_HK
dc.contributor.authorHertzog, PJen_HK
dc.contributor.authorKola, Ien_HK
dc.date.accessioned2010-09-06T09:46:46Z-
dc.date.available2010-09-06T09:46:46Z-
dc.date.issued2003en_HK
dc.identifier.citationBritish Journal Of Cancer, 2003, v. 88 n. 1, p. 137-145en_HK
dc.identifier.issn0007-0920en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88695-
dc.description.abstractEwing's sarcoma is a childhood bone tumour with poor prognosis, most commonly associated with a t(11;22)(q24;q12) reciprocal translocation that fuses the EWS and FLI-1 genes, resulting in the production of an aberrant chimeric transcription factor EWS/FLI-1. To erucidate the mechanisms by which EWS/FLI-1 mediates transformation in mouse models, we have generated a murine Ews/Fli-1 fusion protein. We demonstrate that this protein transforms fibroblast celrs in vitro similar to human EWS/FLI-1 as demonstrated by serum and anchorage-independent growth, the formation of tumours in nude mice and elevation of the oncogenic marker c-myc. Furthermore, transformation of these cells was inhibited by a specific represser, KRAB/FLI-1. The KRAB/FLI-1 repressor also suppressed the tumorigenic phenotype of a human Ewing's sarcoma cell line. These findings suggest that the transformed phenotype of Ewing's sarcoma cells can be reversed by using the sequence-specific FLI-1-DNA-binding domain to target a gone repressor domain. The inhibition of EWS/FLI-1 is the first demonstration of the KRAB domain suppressing the action of an ETS factor. This approach provides potential avenues for the elucidation of the biological mechanisms of EWS/FLI-1 oncogenesis and the development of novel therapeutic strategies. © 2003 Cancer Research UK.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjcen_HK
dc.relation.ispartofBritish Journal of Canceren_HK
dc.subjectEwing's sarcomaen_HK
dc.subjectEWSen_HK
dc.subjectFli-1en_HK
dc.subjectKRABen_HK
dc.subjectRepresseren_HK
dc.titleTransformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-0920&volume=88&spage=137&epage=145&date=2003&atitle=Transformation+induced+by+Ewing%27s+sarcoma+associated+EWS/FLI-1+is+suppressed+by+KRAB/FLI-1en_HK
dc.identifier.emailChan, D:dwchan@hkucc.hku.hken_HK
dc.identifier.authorityChan, D=rp00543en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.bjc.6600669en_HK
dc.identifier.pmid12556973en_HK
dc.identifier.scopuseid_2-s2.0-0037434434en_HK
dc.identifier.hkuros81101en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037434434&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume88en_HK
dc.identifier.issue1en_HK
dc.identifier.spage137en_HK
dc.identifier.epage145en_HK
dc.identifier.isiWOS:000181078900024-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, D=26533900600en_HK
dc.identifier.scopusauthoridWilson, TJ=7403495583en_HK
dc.identifier.scopusauthoridXu, D=7404073425en_HK
dc.identifier.scopusauthoridCowdery, HE=6506404103en_HK
dc.identifier.scopusauthoridSanij, E=6507125632en_HK
dc.identifier.scopusauthoridHertzog, PJ=7005991492en_HK
dc.identifier.scopusauthoridKola, I=7006455084en_HK

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