Transfection of a factor-dependent cell line with the murine interleukin-3 (IL-3) cDNA results in autonomous growth and tumorigenesis.

The factor dependent murine myeloid line 32D c15 was transfected by electroporation with a murine interleukin-3 (IL-3) cDNA expression plasmid bearing the murine metallothionein-I promoter element. Factor-independent cell growth was readily obtained, and was shown to be accompanied by the production of biologically active IL-3. Three cell lines, growing autonomously and secreting IL-3 activity into their supernatants were established. S-1 nuclease analysis was employed to demonstrate that the introduced plasmid and not the endogenous IL-3 gene was the source of the IL-3 in one of these lines. The transfected IL-3 secreting cell lines, but not the parental factor-dependent 32D c15 cells, were uniformly able to induce tumors in syngeneic mice. These results indicate that the conversion to a malignant phenotype of a "partially transformed" cell line may be achieved by one additional dominant genetic event, such as the acquisition of autocrine growth factor secretion.