DIFFERENTIAL-EFFECTS OF VIRAL AND CELLULAR ONCOGENES ON THE GROWTH FACTOR-DEPENDENCY OF HEMATOPOIETIC-CELLS

The effects of different viral and cellular oncogenes on the cytokine-dependency of murine hematopoietic cell lines were compared. The myeloid FDC-P1 cell line was sensitive to abrogation of growth factor-dependency by the constitutive expression of viral oncogenes (v-abl, v-src, v-Ha-ras, and v-fms) and the activated cellular oncogene BCR-ABL and Delta Nraf. The Delta Nraf encoded serine-threonine kinase was approximately 100-fold less efficient in relieving the factor-dependency of FDC-P1 cells than the other oncogenes examined. The synthesis of autocrine cytokines was not detected in the factor-independent FDC-P1 lines, indicating that the oncogene-mediated transformation occurred by a non-autocrine mechanism. A low frequency of cells were isolated after infection with the chronic retrovirus, murine leukemia virus and approximately 40% of these clones synthesized the autocrine lymphokine, granulocyte-macrophage colony stimulating factor. In contrast, only the v-abl and BCR-ABL oncogenes relieved the cytokine-dependency of the lymphoid FL5.12 cell line. In all the transformed cell lines, the rate of glucose transport was elevated above the basal level seen in uninfected cells indicating that this pivotal growth-regulated protein was associated with malignant transformation. In summary, these cell lines varied with respect to abrogation of growth factor-dependency as the myeloid FDC-P1 line was sensitive to transformation by all oncogenes examined whereas only the abl-family members would relieve the cytokine-requirement of lymphoid FL5.12 cells.