c-fos protein can induce cellular transformation: a novel mechanism of activation of a cellular oncogene.

The FBJ murine osteosarcoma virus (FBJ-MuSV) induces tumors in vivo and transformation in vitro. Transformation is due to the expression of a single viral protein (p55v-fos) which is encoded by sequences derived from mouse genetic material. The homologous cellular gene (c-fos) does not transform cultured cells after introduction by transfection. We show that even though the c-fos protein is completely different from the v-fos protein at its C terminus, it is capable of transforming cultured fibroblasts. However, activation of the transforming potential of the c-fos gene requires two manipulations--a transcriptional enhancer sequence must be linked to the gene and an interaction at the 3' end of the gene, which inhibits transformation, must be disrupted. Our studies show that normal cellular protein can induce transformation when expressed in an inappropriate cell type.