EWS/FLI1-induced manic fringe renders NIH 3T3 cells tumorigenic.
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.
May
W A
WA
Department of Pediatrics, University of Alabama at Birmingham School of Medicine, USA.
Arvand
A
A
Thompson
A D
AD
Braun
B S
BS
Wright
M
M
Denny
C T
CT
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005964:Glucosyltransferases; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000209:etiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; D005964:Glucosyltransferases; C486343:Mfng protein, mouse