FOS-TRANSFORMATION ACTIVATES GENES ASSOCIATED WITH INVASION

Fos oncoproteins transform cells by functioning as transcription facto rs. Over-expression of c-fos results in minimal morphological transfor mation while the two viral isolates, FBJ and FBR v-fos, result in full morphological transformation. Fos-transformed cells are serum depende nt for proliferation but not for morphological transformation. To iden tify Fos target genes which might be involved in morphological transfo rmation me screened a cDNA library constructed from RNA isolated from serum starved FBR-transformed cells with cDNA probes prepared from bot h FBR-transformed cells and untransformed parental fibroblasts, 208F. We identified 10 genes which are differentially expressed between FBR and 208F cells. One is a novel gene. Nine are upregulated in c-fos- an d FBJ-transformed cells and also in mutant c-Ha-Ras-transformed 208Fs. All nine of the upregulated genes have been associated previously wit h invasion or metastasis. We demonstrate that the FBR-transformed cell s are invasive in an in vitro assay and that their ability to invade i s enhanced by platelet derived growth factor. We conclude that the fos oncogenes target genes involved in morphological transformation, and invasion.