Examination of the role of CSF-1 independence in myc retrovirus induced monocyte tumorigenesis.
These studies were initiated as an attempt to estimate the number and nature of genetic changes that are required in addition to c-myc deregulation during monocyte tumorigenesis, and to determine whether the oncogenic changes that can be created in vitro resemble the actual changes that occur in vivo. We found that superinfecting myc-immortalized monocytes with a colony stimulating factor-1 (CSF-1) expressing retrovirus strongly promoted tumorigenesis, whereas granulocyte/macrophage-CSF (GM-CSF) and v-fms retroviruses, or the spontaneous acquisition of CSF-1 independence did so only moderately. In addition myc-infected monocytes isolated from mice at a stage prior to tumor formation are more tumorigenic than in vitro myc-immortalized monocytes, but they were still largely CSF-1 dependent, and were not as tumorigenic as reinnoculated tumor cells. In the simplest model only two oncogenic activations are required for monocyte/macrophage transformation, immortalization of the cells with c-myc and deregulation of the CSF-1 gene. However, not all mechanisms that result in loss of CSF-1 dependence lead to full tumorigenicity, suggesting that in vivo tumorigenesis may involve multiple secondary events including growth factor independence.
Eccles
M R
MR
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Baumbach
W R
WR
Cole
M D
MD
D000818:Animals; D001854:Bone Marrow Cells; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016259:Genes, myc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection
D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor