Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abundant expression of MYC can transform both embryonic fibroblasts and hematopoietic cells and elicit granulocytic leukemias in chickens. Transformation by MYC is accompanied by changes in diverse aspects of cellular phenotype, including morphology, ability to grow in suspension, rate of proliferation, the structure of the cytoskeleton, and the composition of the extracellular matrix. Nevertheless, the biological potency ofMYC is inherently constrained when compared to that of the retroviral oncogene v-myc. Our findings enlarge on previous descriptions of neoplastic transformation by MYC and sustain the view that ungoverned expression of the gene can contribute to the genesis of human tumors.The protooncogene MYC was first encountered as the progenitor for the retroviral oncogene v-myc (1, 2). Subsequently, MYC has been implicated in the governance of normal cellular proliferation and differentiation (3) and in the genesis of diverse human tumors (4). Two important questions arose from these findings. What is the tumorigenic potential of normal MYC, and how might damage to MYC augment that potential? The available answers to these questions remain clouded with ambiguity. On the one hand, it is generally agreed that damage to MYC can figure in the genesis of human tumors (4) and that abundant expression of the gene can transform a variety of cells in culture (5-8 (CEFs) or an established line of quail fibroblasts, QT-6, was performed according to published protocols (19). The retroviral vector RCAS was derived from the genome of Rous sarcoma virus (RSV) and was provided by Stephen Hughes (20). A cDNA representing human MYC was inserted into the vector to give the strain RSV(MYC). A molecular clone that expresses the gene for resistance to neomycin under the control of the RSV long terminal repeat was kindly supplied by S. Gerondakis.Stocks of RSV(MYC) were prepared in two ways. (i) DNA of RSV(MYC) was transfected into CEFs and the recipient cells were then propagated en masse until the virus reached high titers. (ii) DNA clones of both RSV(MYC) and the neomycin-resistance vector were cotransfected into QT-6 cells, which, 18 hr later, were suspended in Methocel (5 x 105 cells per 60-mm Petri dish) in the presence of G418 (250 ,ug/ml). Colonies of surviving cells were isolated after -16 days and propagated in the presence of G418 to quantities sufficient for harvesting of viral stocks.The ability of the viral stocks to cause leukemia or hepatomas was tested by injecting standard amounts (200 focusforming units) into the choroallantoic vein of 10-day-old embryos of SPAFAS (Norwich, CT) chickens. To determine sarcomagenic ability, 1-day-old chicks were injected in the wing web. Mortality from the...
