Transformation of murine fibroblasts by a retrovirus encoding the murine c-fms proto-oncogene.
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.
Rohrschneider
L R
LR
Fred Hutchinson Cancer Research Center, Cell Biology Department, Seattle, Washington 98104.
Rothwell
V M
VM
Nicola
N A
NA
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003115:Colony-Stimulating Factors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D051379:Mice; D009374:Neoplasms, Experimental / Q000235:genetics; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface / Q000235:genetics*; D012190:Retroviridae
D003115:Colony-Stimulating Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D016186:Receptor, Macrophage Colony-Stimulating Factor