Abstract
Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abundant expression of MYC can transform both embryonic fibroblasts and hematopoietic cells and elicit granulocytic leukemias in chickens. Transformation by MYC is accompanied by changes in diverse aspects of cellular phenotype, including morphology, ability to grow in suspension, rate of proliferation, the structure of the cytoskeleton, and the composition of the extracellular matrix. Nevertheless, the biological potency of MYC is inherently constrained when compared to that of the retroviral oncogene v-myc. Our findings enlarge on previous descriptions of neoplastic transformation by MYC and sustain the view that ungoverned expression of the gene can contribute to the genesis of human tumors.
MeSH Terms
Actins/analysis
Animals
Avian Sarcoma Viruses/genetics
Cell Division
Cell Transformation, Neoplastic
Cells, Cultured
Chickens
Fibroblasts/cytology
Fibronectins/analysis
Fluorescent Antibody Technique
Genetic Vectors
Humans
Phenotype
Protein-Tyrosine Kinases/genetics
Proto-Oncogene Proteins/genetics
Proto-Oncogene Proteins c-myc
Proto-Oncogenes
Transfection
Chemicals
Actins
Fibronectins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-myc
Protein-Tyrosine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ramsay G M
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Moscovici G
Moscovici C
Bishop J M
References (28)
28 references, click to expand
-
Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29.
J Virol. 1978 Nov;28(2):600-10
PMID: 214581
-
Avian proto-myc genes promoted by defective or nondefective retroviruses are single-hit transforming genes in primary cells.
Proc Natl Acad Sci U S A. 1989 Oct;86(20):7721-5
PMID: 2554285
-
Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation.
Cell. 1979 Oct;18(2):375-90
PMID: 227607
-
Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.
Nature. 1983 Aug 18-24;304(5927):596-602
PMID: 6308472
-
Quail embryo fibroblasts transformed by four v-myc-containing virus isolates show enhanced proliferation but are non tumorigenic.
EMBO J. 1983;2(12):2385-9
PMID: 6321165
-
Subcellular localization of proteins encoded by oncogenes of avian myeloblastosis virus and avian leukemia virus E26 and by chicken c-myb gene.
Cell. 1984 Jun;37(2):537-47
PMID: 6327074
-
New procedure for DNA transfection with polycation and dimethyl sulfoxide.
Mol Cell Biol. 1984 Jun;4(6):1172-4
PMID: 6330534
-
Rous sarcoma virus variants that carry the cellular src gene instead of the viral src gene cannot transform chicken embryo fibroblasts.
Proc Natl Acad Sci U S A. 1984 Jul;81(14):4424-8
PMID: 6087323
-
Biological activities of v-myc and rearranged c-myc oncogenes in rat fibroblast cells in culture.
Proc Natl Acad Sci U S A. 1984 Sep;81(18):5758-62
PMID: 6091107
-
Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes.
Cell. 1984 Oct;38(3):627-37
PMID: 6488314
-
Fibroblast lines expressing activated c-myc oncogenes are tumorigenic in nude mice and syngeneic animals.
Cell. 1984 Dec;39(2 Pt 1):339-48
PMID: 6498938
-
The protein encoded by the human proto-oncogene c-myc.
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7742-6
PMID: 6393124
-
Sequence curiosity in v-myc oncogene.
Nature. 1985 Nov 21-27;318(6043):237
PMID: 4069201
-
The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice.
Nature. 1985 Dec 12-18;318(6046):533-8
PMID: 3906410
-
Transformation of quail embryo fibroblasts by a retrovirus carrying a normal human c-myc gene.
EMBO J. 1986 Jul;5(7):1529-33
PMID: 3017699
-
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
Mol Cell Biol. 1985 Dec;5(12):3610-6
PMID: 3915782
-
Tumorigenicity of fibroblast lines expressing the adenovirus E1a, cellular p53, or normal c-myc genes.
Mol Cell Biol. 1986 Jan;6(1):7-14
PMID: 2946931
-
High mutation rate of a spleen necrosis virus-based retrovirus vector.
Mol Cell Biol. 1986 Dec;6(12):4387-95
PMID: 3796606
-
The molecular genetics of cancer.
Science. 1987 Jan 16;235(4786):305-11
PMID: 3541204
-
The myc oncogene: its role in transformation and differentiation.
Annu Rev Genet. 1986;20:361-84
PMID: 3028245
-
Neoplastic transformation by the human gene N-myc.
Mol Cell Biol. 1987 May;7(5):1638-45
PMID: 3299052
-
Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors.
J Virol. 1987 Oct;61(10):3004-12
PMID: 3041020
-
The effect of alterations in myc gene expression on B cell development in the bursa of Fabricius.
Cell. 1987 Nov 6;51(3):371-81
PMID: 3499231
-
Transgenic mice and oncogenesis.
Annu Rev Immunol. 1988;6:25-48
PMID: 2838049
-
The transforming activity of the chicken c-myc gene can be potentiated by mutations.
Oncogene. 1987;1(4):415-22
PMID: 3330784
-
Transformation of murine myelomonocytic cells by myc: point mutations in v-myc contribute synergistically to transforming potential.
Oncogene. 1989 Mar;4(3):285-94
PMID: 2649846
-
Regulation of cell cycle duration by c-myc levels.
Oncogene. 1989 Jun;4(6):773-87
PMID: 2660073
-
Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation.
Nature. 1979 Oct 11;281(5731):452-5
PMID: 226888