The proto-oncogene FGF-3 is constitutively expressed in tumorigenic, but not in non-tumorigenic, clones of a human colon carcinoma cell line.
The human colon carcinoma cell line, SW613-S, is composed of cells with a high-level amplification of the MYC proto-oncogene that are tumorigenic in nude mice and of cells with a low-level amplification of MYC that are not tumorigenic. Transcripts from FGF-3, a member of the fibroblast growth factor gene family, accumulate in cells from tumorigenic clones, but are undetectable in those from non-tumorigenic clones. Nuclear run-on analyses indicate that this differential FGF-3 expression is regulated at the level of transcription initiation. Determination of the structure of the FGF-3 transcripts indicates that they are generated by splicing of the three exons and termination at the single polyadenylation site predicted from the genomic sequence. Their size heterogeneity is due to multiple initiation sites spanning a 700 base-pair long promoter region. FGF-3 is activated in tumors induced in nude mice by MYC-transfected cells from non-tumorigenic clones. However, in most of the cell lines established from these tumors, FGF-3 expression tends to be lost upon in vitro propagation. Thus, in these transfectant cell lines, the presence of exogenous MYC gene copies is not sufficient to activate FGF-3 expression and in vivo growth is also required.
Galdemard
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Laboratoire de Génétique Oncologique, URA 1967 CNRS, Institut Gustave Roussy, Villejuif, France.
Brison
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Lavialle
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D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000199:Actins; C496444:FGF3 protein, human; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors