Abstract
EWS/FLI1, a fusion gene found in Ewing's sarcoma, encodes a transcriptional regulator and promotes cellular transformation by modulating the transcription of specific target genes. We have found that EWS/FLI1 and structurally related fusion proteins upregulate manic fringe (MFNG), a recently described member of the Fringe gene family instrumental in somatic development. MFNG is also expressed in human tumour-derived cell lines expressing EWS/FLI1. Overexpression of MFNG in NIH 3T3 cells renders them tumorigenic in mice with severe combined immunodeficiency disease (SCID). These data demonstrate that part of the oncogenic effect of EWS/FLI1 is to transcriptionally deregulate a member of a family of morphogenic genes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Cell Transformation, Neoplastic / genetics*
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Gene Expression Regulation, Neoplastic
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Glucosyltransferases
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Mice
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Mice, SCID
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Neoplasm Transplantation
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / physiology*
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Protein Biosynthesis
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Proteins / genetics*
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Proto-Oncogene Protein c-fli-1
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RNA-Binding Protein EWS
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Sarcoma, Ewing / etiology
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Sarcoma, Ewing / genetics*
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Tumor Cells, Cultured
Substances
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EWS-FLI fusion protein
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Oncogene Proteins, Fusion
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Proteins
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Proto-Oncogene Protein c-fli-1
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RNA-Binding Protein EWS
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Transcription Factors
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Glucosyltransferases
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Mfng protein, mouse