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 sp ontaneous feline T-cell lymphosarcoma, Molecular cloning and sequencin g of the v-myc gene revealed several unique mutations, including a lar ge deletion affecting amino acids 49 to 124 and a 3-bp insertion withi n 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 pro tein 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 eviden ce that the T17 mutant gene retains oncogenic potential was provided b y its detection in clonally integrated proviruses in secondary tumors induced by feline leukemia virus T17, where no reversion mutations wer e found in any of three tumors examined, However, the mutant T17 v-myc gene did not induce transformation in a chicken embryo fibroblast ass ay, in contrast to wild-type feline c-myc, which conferred higher grow th rates on the chicken fibroblasts, along with altered morphology and the ability to form foci in soft agar, Chicken cells overexpressing f eline c-myc died by apoptosis when cultured with low serum concentrati ons, while the T17 mutant had no discernible effect, These results sug gest 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 sens itive to a subset of Myc functions which are insufficient for fibrobla st transformation.