A 3' truncation of myc caused by chromosomal translocation in a human T-cell leukemia is tumorigenic when tested in established rat fibroblasts.
We have previously identified in human T-leukemia cells a myc gene with an unusual 3' rearrangement, and we have shown that expression of the gene is deregulated by stabilization of mRNA. Here we report that the rearranged gene transforms established rat fibroblasts to a tumorigenic phenotype. In hybrid genes, the transforming capability segregates with the 3' rearrangement. Transformation is apparently due to a more than fivefold enhancement in myc expression, attributable to stabilization of mRNA. The rearranged allele of myc also contains a point mutation in a region upstream of the gene, identified previously as a potential negative regulator of myc expression. The mutation may increase expression of myc, but not sufficiently to cause cellular transformation. Our findings enlarge the variety of genetic lesions that may activate myc to an oncogene and sustain the view that augmented expression of an otherwise normal allele of myc can be pathogenic.
Aghib
D F
DF
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Bishop
J M
JM
D000483:Alleles; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000166:cytology; D015321:Gene Rearrangement; D016259:Genes, myc; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014162:Transfection; D014178:Translocation, Genetic
D012333:RNA, Messenger