V-MYC IS INVARIABLY REQUIRED TO SUSTAIN RAPID PROLIFERATION OF INFECTED-CELLS BUT IN STABLE CELL-LINES BECOMES DISPENSABLE FOR OTHER TRAITSOF THE TRANSFORMED PHENOTYPE

The v-myc-containing retrovirus MC29 induces neoplastic transformation of avian embryo cells. To determine which traits of the transformed p henotype are directly controlled by v-Myc, we engineered a conditional MC29 mutant (GRIM) expressing v-Myc as a fusion protein with the gluc ocorticoid receptor and the retroviral Gag polyprotein. Only in the pr esence of glucocorticoids such as dexamethasone is GRIM capable of tra nsforming embryo cells, from which six stable GRIM-lines have been der ived. Although their survival in culture no longer requires functional v-Myc, hormone deprivation causes all six GRIM clones as web as acute ly infected fibroblast cultures to either withdraw from cell cycle com pletely or to grow much more slowly and to much lower densities. Howev er, removal of dexamethasone does not allow GRIM-transformed mass cult ures and most of the clones to revert to normal shapes or to reconstru ct actin cables. Furthermore, most clones do not require the hormone s ustain anchorage-independent growth. We propose that certain secondary events have let the GRIM-clones sustain immortality, transformed morp hology, and anchorage-independent growth independently of v-Myc. None of these events, however, has obliterated the requirement for v-Myc in cell division control. We thus conclude that enhanced proliferation i s the primary effect of v-Myc expression.