title: Recombinant BALB and Harvey sarcoma viruses with normal proto-ras-coding regions transform embryo cells in culture and cause tumors in mice.
abstract: The ras genes of BALB and Harvey sarcoma viruses contain point mutations in codon 12 or codons 12 and 59, relative to proto-ras from normal animal and human cells. By in vitro recombination between cloned rat proto-ras and cloned BALB and Harvey sarcoma proviruses, we constructed recombinant proviruses with normal proto-ras-coding regions. These recombinant proviruses transformed mouse 3T3 cells upon transfection. However, when the transforming efficiencies of proviral DNAs were compared after transfection with helper provirus, recombinant proviruses were 2 to 30 times less efficient than the corresponding wild-type proviruses. Recombinant sarcoma viruses isolated from cells transformed by cloned proviral DNA contained the expected normal ras-coding region. They transformed rat embryo cells and induced erythroblastosis and sarcomas in newborn mice as efficiently as wild-type viruses did. We conclude that conversion of normal proto-ras genes to viral ras genes depends on truncation of normal proto-ras regulatory elements and substitution by retroviral (long terminal repeat) promoters and that the transforming function of long terminal repeat-ras genes is enhanced by point mutations.
authors.affiliation: Department of Molecular Biology, University of California, Berkeley 94720.
authors.forename: K
authors.initials: K
authors.lastname: Cichutek
authors.forename: P H
authors.initials: PH
authors.lastname: Duesberg
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003062:Codon; D004900:Erythroblasts; D005786:Gene Expression Regulation; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011519:Proto-Oncogenes; D051381:Rats; D009053:Sarcoma Viruses, Murine / Q000235:genetics / Q000472:pathogenicity*; D012513:Sarcoma, Experimental / Q000235:genetics
chemical_list: D003062:Codon; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras)