The avian acute leukemia virus, E26, expresses oncogenic fusion proteins containing portions of the myb and ets-1 genes derived from the avian genome. In order to study both the normal and oncogenic functions of these genes, particularly ets, we have developed a murine model for myb-ets oncogenesis by introducing the gag-myb-ets coding sequences from E26 into a murine retroviral vector. This defective murine viral construct (ME26) induces leukemia in newborn mice and abrogates the serum dependence for growth of NIH3T3 murine fibroblasts. We have now analyzed the expression of serum-response genes in NIH3T3 fibroblasts which have lost their dependence on serum for growth following infection of ME26. No increase in fos, jun or myc expression was seen in ME26-infected cells in comparison to uninfected 3T3 cells, and expression in ME26-infected hematopoietic cells was also not altered. Likewise, c-ets-I and c-ets-2 endogenous expression was not increased in these cells. These results suggest that ME26 may induce serum-independent growth in fibroblasts by a mechanism that does not involve the serum-response pathway. We have also detected a novel 3.7 kb subgenomic ME26 message in both infected fibroblasts and hematopoietic cells in culture. The subgenomic message contains both myb and v-ets specific sequences and is not incorporated into viral particles. The coding potential of this subgenomic message remains to be determined.
