The ras and myc oncogenes cooperate in tumor induction in many tissues when introduced into midgestation mouse embryos by retroviral vectors.
Midgestation embryos were infected with replication-defective retroviral vectors that either transduced the myc oncogene, the ras oncogene, or both oncogenes simultaneously. The myc virus induced tumors in diverse organs at a very low frequency and with a long latency period, while approximately 20% of the mice derived from embryos infected with the ras virus developed tumors in the skin with a latency of 4-8 weeks. In contrast, infection of embryos with the ras/myc double oncogene virus resulted in 27% of the animals developing rapidly growing and malignant tumors in a great variety of tissues after a median latency period of 2-3 weeks. All tumors were of monoclonal origin, as shown by Southern analysis using the provirus as a molecular marker. Our results are consistent with the hypothesis that the ras and myc oncogenes cooperate in transforming cells, but that additional alterations are necessary for realization of the fully malignant phenotype. Our observations also suggest that a much wider range of cell types become targets for malignant transformation when the embryos are exposed to the myc and the ras oncogenes simultaneously than when exposed to the same oncogenes separately. Infection of mouse embryos with vectors carrying different oncogenes or oncogene combinations may be an efficient and rapid method for evaluating the spectrum of cell types at risk for malignant conversion following mutation of a protooncogene to a transforming gene.
Compere
S J
SJ
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Baldacci
P
P
Sharpe
A H
AH
Thompson
T
T
Land
H
H
Jaenisch
R
R
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D004622:Embryo, Mammalian; D011905:Genes, ras; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011519:Proto-Oncogenes; D012190:Retroviridae / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D014161:Transduction, Genetic