Transformation of murine myelomonocytic cells by myc: point mutations in v-myc contribute synergistically to transforming potential.
The v-myc oncogenes of chicken retroviruses (including MC29) bear point mutations relative to chicken c-myc. These mutations result in several amino acid differences in the encoded proteins. We have used recombinant murine retroviruses containing various myc alleles to analyse the myelomonocytic transforming potential of the myc oncogene. The myc alleles used were MC29 v-myc, chicken c-myc, chimeric genes combining 5' sections of v- or c-myc with 3' sections of c- or v-myc, and mouse c-myc. The same retroviral vector (based on the genome of Moloney leukemia virus) was used for each allele and the genes were translated from genomic message. By infecting the primary mouse tissues, bone marrow, peritoneal-derived macrophages and mixed embryonic tissue with the recombinant viruses, variation was found in the transforming efficacy of these alleles: v-myc was most effective, followed by the two chimeric genes, whereas c-myc (chicken or mouse) was least effective in eliciting myelomonocytic transformation. Viral gag sequences were not necessary for this transformation. In each case, the transformed monocytes were growth factor-dependent and non-immortal. However, v-myc transformed monocytes (though not monocytes transformed by other myc alleles) were able to progress to an immortal, growth factor-independent phenotype. Our results indicate that v-myc is far more effective than c-myc in eliciting myelomonocytic transformation; that this is due to combinatorial effects of 5' and 3' mutations in the v-myc gene; and that secondary events in addition to these mutations are required for transformation of myelomonocytic cells to an immortal, tumorigenic phenotype.
Symonds
G
G
Children's Medical Research Foundation, Camperdown, N.S.W., Australia.
Hartshorn
A
A
Kennewell
A
A
O'Mara
M A
MA
Bruskin
A
A
Bishop
J M
JM
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D016274:Oncogene Protein p55(v-myc); D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc; D012191:Retroviridae Proteins / Q000502:physiology*
D016274:Oncogene Protein p55(v-myc); D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012191:Retroviridae Proteins