RNA-TUMOR VIRUS--HEMATOPOIETIC CELL INTERACTION

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Many retroviruses induce tumors when injected into appropriate hosts and thus are useful tools to study the events controlling the oncogenic process. Rapidly transforming viruses are particularly well suited to such studies because they seem to cause tumors by directly interfering with normal growth and differentiation. Generally, these viruses have lost most or all of the genes of replication competent retroviruses and acquired sequences closely related to normal cellular DNA called on cosequences or onc genes. Although formal proof is lacking in many cases, the expression of these viral onc genes appears to be responsible for the virus' ability to induce tumors and transform cells. Although the products of onc genes were originally identified by their ability to induce tumors and transform cells, recent evidence indicates that expression of the same "transforming" protein in different cell types can have different effects. For example, although Abelson virus infection of some hematopoietic cells induces transformation of lymphoid cells, infection of hematopoietic cells derived from early embryonic tissues induces growth and differentiation of erythroid cells. In addition, although A-MuLV transforms some fibroblastoid cell lines, the virus is lethal to others. The mode of action of viral onc genes and the role the normal sequences from which they were derived may play in growth and differentiation are presently unclear. Examination of this question is an important step toward achieving an understanding of the mechanism of oncogenesis by rapidly transforming retroviruses. In addition, an understanding of the mechanism(s) by which normal cellular information is subverted, leading to the development of malignancy, has implication beyond retrovirus-cell interaction. To address this question, we have chosen to study a hematopoietic cell model system and examine the consequences of expression of two unrelated onc proteins, P160 v-ab1, encoded by Abelson murine leukemia virus and P21 v-ras, encoded by Harvey murine sarcoma virus.