A mouse c-myc retrovirus transforms established fibroblast lines in vitro and induces monocyte-macrophage tumors in vivo

Abstract

Activation of the c-myc proto-oncogene, in the form of DNA rearrangements that lead to constitutive expression, has been implicated in the genesis of a wide range of tumors. Therefore, it is of great interest to determine the influence of c-myc oncogene activation on cellular growth control, especially in primary cells. To facilitate the efficient transfer of an activated c-myc oncogene, we developed a mouse retrovirus that contains the c-myc protein-coding sequences and which can be transmitted in the presence of a Moloney murine leukemia virus helper or established as a helper-free stock with a retrovirus-packaging cell line. The virus can transform established lines of mouse fibroblasts to anchorage-independent growth; the transformed cells are tumorigenic in nude mice. However, the virus was not capable of inducing foci of transformed cells on confluent monolayers. In addition to studies on established cell lines, the effect of the c-myc retrovirus on primary cells was examined. Infection of bone marrow cells gave rise to partially transformed mononuclear phagocytes which were entirely dependent upon an exogenous supply of the monocyte-specific colony-stimulating factor CSF-1 for proliferation. Infection in vivo induced monocyte-macrophage tumors with a latency period of 8 to 10 weeks.