Transformation of murine fibroblasts by a retrovirus encoding the murine c-fms proto-oncogene

Abstract

The c-fms proto-oncogene is the growth factor receptor for the macrophage colony stimulating factor, M-CSF. In this paper we have investigated the inappropriate expression of c-fms within a species as a relevant model for analysing transformation, growth, and differentiation promoting activities of c-fms. A retroviral vector was constructed for the expression of the murine c-fms proto-oncogene in murine cells. Initial characterization of this vector was performed in fibroblasts. Infection of Balb/c 3T3 cells with the murine c-fms retrovirus resulted in high level expression of the gp140c-fms precursor and the gp165c-fms mature receptor protein on the cell surface and both proteins exhibited kinase activity. Up to 3.3 x 10(4) M-CSF receptors per cell were detectable. The c-fms retrovirus induced foci of morphologically transformed Balb/c cells that exhibited anchorage independent growth in soft agar and produced progressively growing tumors in syngeneic animals. The Balb/c cells synthesize and secrete M-CSF and therefore these results suggest an autocrine mechanism of transformation caused solely by the expression of a normal growth factor receptor in an inappropriate, endogenous M-CSF-producing cell.