The ras and myc oncogenes cooperate in tumor induction in many tissues when introduced into midgestation mouse embryos by retroviral vectors
Autor: | Patricia Baldacci, Timothy C. Thompson, Arlene H. Sharpe, Rudolf Jaenisch, Hartmut Land, Sally J. Compere |
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Rok vydání: | 1989 |
Předmět: |
Proto-Oncogenes
Cell type Skin Neoplasms Genetic Vectors Mice Inbred Strains Biology medicine.disease_cause Virus Malignant transformation Mice Transduction Genetic medicine Animals Mutation Mice Inbred BALB C Multidisciplinary Oncogene Malignant Conversion Brain Neoplasms Provirus Embryo Mammalian Mice Inbred C57BL Cell Transformation Neoplastic Genes ras Retroviridae Cancer research Carcinoma Squamous Cell Research Article |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 86(7) |
ISSN: | 0027-8424 |
Popis: | 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. |
Databáze: | OpenAIRE |
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