v-Myc is invariably required to sustain rapid proliferation of infected cells but in stable cell lines becomes dispensable for other traits of the transformed phenotype.
The v-myc-containing retrovirus MC29 induces neoplastic transformation of avian embryo cells. To determine which traits of the transformed phenotype are directly controlled by v-Myc, we engineered a conditional MC29 mutant (GRIM) expressing v-Myc as a fusion protein with the glucocorticoid receptor and the retroviral Gag polyprotein. Only in the presence of glucocorticoids such as dexamethasone is GRIM capable of transforming embryo cells, from which six stable GRIM-lines have been derived. Although their survival in culture no longer requires functional v-Myc, hormone deprivation causes all six GRIM clones as well as acutely infected fibroblast cultures to either withdraw from cell cycle completely or to grow much more slowly and to much lower densities. However, removal of dexamethasone does not allow GRIM-transformed mass cultures and most of the clones to revert to normal shapes or to reconstruct actin cables. Furthermore, most clones do not require the hormone sustain anchorage-independent growth. We propose that certain secondary events have let the GRIM-clones sustain immortality, transformed morphology, 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 is the primary effect of v-Myc expression.
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D003370:Coturnix; D016259:Genes, myc; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D011993:Recombinant Fusion Proteins
D009838:Oligodeoxyribonucleotides; D016274:Oncogene Protein p55(v-myc); D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins