Identification of a MMTV insertion mutation within the coding region of the Fgf-3 protooncogene.
The Fgf-3 protooncogene (previously called int-2) is a target of proviral insertion mutations in mammary tumors induced by the mouse mammary tumor virus (MMTV). These insertion mutations result in the transcriptional activation of Fgf-3, which is not normally expressed in the adult mammary gland. Previous mapping studies of numerous Fgf-3 insertion mutations have failed to reveal any provirus integrations within the gene coding region. This finding is consistent with the hypothesis that oncogenesis occurs in this system as a consequence of up-regulation of Fgf-3 transcription, rather than from alterations of the gene product. During an analysis of a new cohort of tumors from the WXG-2 mouse strain, a breast tumor was identified which had a MMTV provirus integrated 24 bp upstream of the Fgf-3 stop codon. This insertion mutation generated a fusion transcript which was readily detectable in tumor RNA by RT-PCR. The predicted protein product of this fusion transcript is missing 8 aa of native sequence and contains an additional 8 aa of cryptic MMTV-encoded sequence. These data document the first exception to the generalization that the Fgf-3 coding region is not disrupted by MMTV insertion mutation.
Morris
D W
DW
Department of Medical Pathology, University of California, Davis 95616, USA. dwmorris@ucdavis.edu
Dutra
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004251:DNA Transposable Elements; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000821:virology; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D011519:Proto-Oncogenes; D011533:Proviruses / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004251:DNA Transposable Elements; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors