Activation of the M-CSF gene in mouse macrophages immortalized by retroviruses carrying a v-myc oncogene.

We have recently immortalized murine brain macrophages (microglial cells) with a complex of retroviruses (3RV) transducing separately the myc and mil oncogenes. Surprisingly, the immortalized cells harboured an exogenous v-myc oncogene, but no v-mil sequences. The transformed macrophage cell lines grew in vitro without the addition of exogenous growth factors and were also able to grow in vivo in nude mice. In addition, they released oncogenic retroviruses able to immortalize mouse macrophages from primary splenic or thymic cultures. Molecular cloning of the provirus (VN-11) harboured in a microglial clone demonstrated that no cell-derived sequences apart from an avian v-myc gene were transduced by the recombinant retrovirus. When cells were tested for production of myeloid growth factors, they were found to transcribe and synthesize the Macrophage-Colony Stimulating Factor (M-CSF). The correlation between viral infection and activation of the M-CSF gene was tested using a M-CSF dependent cell line from which growth factor independent clones could be readily obtained after infection. The synthesis of M-CSF was detected only in cells expressing the avian v-myc protein. These data support the hypothesis that, in our conditions, macrophages can be immortalized by the expression of v-myc and the concomitant establishment of an autocrine loop triggered by viral infection.