Transformation and Insertional Mutagenesis In Vitro of Primary Hematopoietic Stem Cell Cultures
Deregulated expression of proto-oncogenes alone or in concert appears to be causally related to the development of many neoplasias in vertebrates. We have previously shown that the combination of two oncogenes, v-raf and v-myc, in an infectious murine retrovirus (the J-2 virus) is cumulative in terms of the types of tumors that are induced and synergistic in terms of the latencies with which the tumors develop relative to those induced by retroviruses carrying only v-raf and v-myc (Rapp et al., 1985b; Cleveland et al., 1986). Specifically, the v-raf carrying viruses, 3611 and J-l, induce fibrosarcomas and erythroid hyperplasia (Rapp et al., 1983a, 1983b, 1985b), whereas v-myc expressing viruses (J-3 and J-5) induce T and B cell lineage lymphomas, and more rarely, pancreatic and mammary carcinomas (Morse et al., submitted). The dual oncogene retrovirus, J-2, induced all of these neoplasms with a greatly reduced latency. Moreover, mice inoculated with J-2 virus generally die of multiple neoplasias. However, all neoplasms induced by this recombinant virus were clonal or oligoclonal in nature, suggesting that even the deregulated expression of two oncogenes was perhaps insufficient to maintain the transformed state and that unidentified additional events were also necessary.
KeywordsMast Cell Insertional Mutagenesis Helper Virus Mast Cell Line Myeloid Leukemia Cell Line
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