The oncogenic and growth-altering properties of a replication-defective murine retrovirus construct, ME26, which expresses the gag-myb-ets fusion oncogene of the avian acute leukemia virus, E26, is being utilized to study the oncogenic potential of myb and ets in mammalian systems, and the role of myb and ets in normal and abnormal growth and development. A drug-selectable version of this virus (MA26) has been developed, and it has been shown that, like its ME26 homolog, it induces FDC-P2 cells, a murine IL3-dependent, bone marrow-derived cell line, to grow in the erythroid hormone erythropoietin (epo) in place of IL3. The relative number of FDC-P2 cells in a drug-selected pool of MA26-infected cells is low, despite the expression of high levels of viral message. These results suggest additional cell and viral factors are necessary to induce epo responsiveness in FDC-P2 cells in culture. MA26 was used to induce epo-dependent growth in other murine IL3-dependent cell lines. Only those cells which express detectable levels of the erythroid-specific transcription factor GATA-1 are able to grow in epo following MA26 infection. This indicates that MA26 cannot induce de novo expression of GATA-1 and the epoR, and suggests the target of gag-myb-ets-induced erythroleukemia may be an erythroid-committed, GATA-1-expressing cell. It was also observed that FDC-P1 cells, a promyelocytic IL3-dependent murine cell line, becomes factor-independent following MA26 or ME26 infection. This appears to occur by an autocrine mechanism, since a factor sensitive to anti-IL3 antibodies is released into the culture fluid by MA26- infected, factor-independent FDC-P1 cells. These results suggest that in the appropriate cell background, the gag-myb-ets fusion oncogene can affect the expression of IL3.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Division of Cancer Epidemiology and Genetics
United States
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