A murine homolog of the avian acute leukemia virus, E26, was used to study the oncogenic and growth-altering potential of the gag-myb-ets fusion oncogene and its constituent myb and ets components. Expression of this virus in some, but not all, IL3-dependent murine hematopoietic cell lines leads to these cells acquiring the potential to grow on epo (erythropoietin), and to express elevated levels of GATA-1, the epo receptor, and beta-globin. The steps and requirements necessary for a cell to acquire an epo-responsive phenotype are being analyzed. The data suggests that additional steps are required for a cell to become able to grow on epo, in addition to gag-myb-ets expression, and that some of the effects appear to be reversibly dependent on the presence of epo. Additional evidence that v-ets/DNA interactions are essential for fusion protein induction of changes in fibroblast growth factor dependence has been obtained. ELF, a gene whose product blocks the expression of ets- responsive promoters, is able to inhibit the low-serum growth of cells expressing the ME26 oncogene, consistent with earlier studies which indicated that deletion of the v-ets DNA-binding domain inactivated the capacity of the virus to induce low-serum proliferation of 3T3 fibroblasts.
