Induction of proliferation or transformation of neuroretina cells by the mil and myc viral oncogenes.

The genome of the avian retrovirus MH2 contains, in addition to the v-myc oncogene shared with three other avian retroviruses (MC29, CMII and OK-10), a second cell-derived oncogene, v-mil (refs 1-3). Like the three other viruses, which contain only v-myc, MH2 induces mainly liver and kidney carcinomas in fowl and transforms fibroblasts and macrophages in vitro. However, MH2 and MC29 differ in their biological properties when assayed on cultures of chicken embryo neuroretina (NR) cells. Indeed, NR cells, which normally do not multiply in vitro, are induced to proliferate and become transformed upon infection with MH2, whereas infection with MC29 has no apparent effect on these cells. To analyse the functions of the two oncogenes of MH2, we isolated spontaneous and in vitro-constructed mutants of this virus and investigated their effects on NR cell multiplication and transformation. We report here that expression of v-mil is sufficient to induce NR cell proliferation, although it does not result in cell transformation. In addition, viruses expressing only the v-myc oncogene fail to induce any detectable change in NR cells. However, cooperation of the two oncogenes is required to achieve transformation of NR cells by MH2.