REGULATION OF C-FOS EXPRESSION IN A TRANSFORMED-CELL LINE CAPABLE OF REVERSION TO THE PSEUDONORMAL PHENOTYPE

The regulation of c-fos gene expression was studied in two mouse sarco ma CBA and C3H lines of spontaneous origin. Each cell line was represe nted by a highly tumorigenic clone capable of initiating rapidly growi ng solid tumors in syngenic mice and possessing a transformed phenotyp e, and also a nontumorigenic clone. The latter was obtained from the f ormer by cloning a revertant to the pseudonormal phenotype. The expres sion of c-fos m-RNA in revertants to the pseudonormal phenotype did no t differ from its expression in normal fibroblasts. In experiments wit h transient and permanent transfection of pseudonormal phenotype cells with indicator plasmid fos-cat, it was found that the 600-bp c-fos pr omoter including the TATA site provides a chloramphenicol acetyltransf erase (CAT) expression level that correlates with c-fos mRNA expressio n. In the tumorigenic line a high constitutive CAT gene activity was o bserved, which was comparable to that of normal fibroblasts stimulated by embryonal serum. The activity of transcription factors that intera ct with the serum content-regulated element (SRE), the double symmetry element (DSE), and the TPA-regulated element (TRE) (all located in th e c-fos promoter) did not correlate with the level of c-fos mRNA expre ssion.