Expression of a Hemopoietic Growth Factor CDNA in a Factor-dependent Cell Line Results in Autonomous Growth and Tumorigenicity

Production of a growth factor by a cell that responds to this factor has been termed "autocrine" stimulation of proliferation. Considerable experimental data have suggested that tumor cells often exhibit autocrine growth stimulation and that this may contribute to the process of malignant transformation. To experimentally approach the relationship of autocrine growth stimulation to the malignant transformation of hemopoietic cells, we have used a retroviral vector to express sequences encoding a hemopoietic growth factor, granulocyte-macrophage colony stimulating factor (GM-CSF) in a factor-dependent murine cell line (FDC-P1). Virally infected cells synthesized and secreted GM-CSF, grew independently of exogenous CSF, and--unlike the parental FDC-P1 cells--produced tumors in syngeneic mice. We have thus experimentally induced autocrine growth regulation in a factor-dependent hemopoietic cell line and have shown that this results in tumorigenicity.