Apparent uncoupling of oncogenicity from fibroblast transformation and apoptosis in a mutant myc gene transduced by feline leukemia virus.
The T17 v-myc oncogene was transduced by feline leukemia virus in a spontaneous feline T-cell lymphosarcoma. Molecular cloning and sequencing of the v-myc gene revealed several unique mutations, including a large deletion affecting amino acids 49 to 124 and a 3-bp insertion within the basic DNA binding domain which converts Leu-362 to Phe-Arg. The T17 lymphoma cell line was found to express a truncated 50-kDa Myc protein at exceptionally high levels, while the endogenous c-myc gene was not detectably expressed. These observations suggest that the mutant Myc product expresses an oncogenic function in T cells. Further evidence that the T17 mutant gene retains oncogenic potential was provided by its detection in clonally integrated proviruses in secondary tumors induced by feline leukemia virus T17, where no reversion mutations were found in any of three tumors examined. However, the mutant T17 v-myc gene did not induce transformation in a chicken embryo fibroblast assay, in contrast to wild-type feline c-myc, which conferred higher growth rates on the chicken fibroblasts, along with altered morphology and the ability to form foci in soft agar. Chicken cells over-expressing feline c-myc died by apoptosis when cultured with low serum concentrations, while the T17 mutant had no discernible effect. These results suggest that the leukemogenic potential of Myc can be uncoupled from its ability to cause transformation in fibroblasts. A possible explanation for this apparent paradox is that developing T cells are acutely sensitive to a subset of Myc functions which are insufficient for fibroblast transformation.
Fulton
R
R
Department of Veterinary Pathology, University of Glasgow, Bearsden, Scotland.
Gallagher
R
R
Crouch
D
D
Neil
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D002415:Cats; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D016259:Genes, myc / Q000235:genetics*; D005256:Leukemia Virus, Feline / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors