Synergy between SCF or M-CSF with IL-3 or GM-CSF in FDC-P1 cells: a sensitive assay of transforming mutations of c-fms

Abstract

Stem cell factor (SCF) was found to stimulate the growth of the haemopoietic cell line FDC-P1 in synergy with either interleukin 3 (IL-3) or granulocyte-macrophage-colony stimulating factor (GM-CSF). Similarly, macrophage colony-stimulating factor (M-CSF) was shown to synergize with IL-3 or GM-CSF, following the infection of FDC-P1 cells with a recombinant retrovirus which encoded the receptor for M-CSF (M-CSFr). These results raise the possibility that signal transduction pathways which are controlled by SCF in FDC-P1 cells, can be activated by M-CSF if its receptor is illicitly expressed. FDC-P1 cells that expressed the M-CSFr were responsive to as little as 100 U/ml of M-CSF when added in combination with IL-3 or GM-CSF. This sensitive assay was used to demonstrate that transforming deletions of the C-terminal tail of the M-CSFr and two-point mutations within the same region that converted tyrosine 969 to either phenylalanine or to cysteine, allowed the mutant M-CSF receptors to synergize with IL-3 or GM-CSF in the absence of M-CSF. These mutations were found to be more evidently transforming in FDC-P1 cells than in Rat-2 fibroblasts. The possible relevance of these results to leukaemia and to gynaecological malignancies is discussed.