c-fos gene expression in cell revertants from a transformed to a pseudonormal phenotype.

c-fos gene expression in two types of mouse sarcoma cells of spontaneous origin and in revertants to pseudonormal phenotype has been investigated. In the latter cells the content of c-fos mRNA is similar to that in normal fibroblasts. Activity of transcription factors interacting with the regulatory elements, SRE, DSE and TRE, in the c-fos promoter do not correlate with the c-fos mRNA concentration. However, experiments with cells transformed with the indicator plasmid, fos-CAT, showed that the 600 bp c-fos promoter region provides the chloramphenicol acetyltransferase activity correlating with c-fos mRNA expression in cell revertants to a pseudonormal phenotype.

High frequency of tumour cell reversion to non-tumorigenic phenotype.

Nine spontaneously transformed cell lines were isolated from embryo fibroblasts of mice and rats with different genotypes. In six cell lines highly tumorigenic cell variants were selected. At the start of culture all cell lines were of low or zero tumorigenicity. The same cells in a confluent monolayer in vitro had high contact inhibition of growth and proliferated in response to stimulation by growth factors. Tumour progression of the established lines was accompanied by significant changes of these properties. Clonal analysis of the six most malignant cell lines revealed their capacity to revert simultaneously to the non-tumorigenic state and to their initial growth characteristics. Frequencies of reversion to the non-tumorigenic phenotype were much higher than re-reversion to the tumorigenic phenotype. The reversions occurred in several sequential passages of transformed clones, with some variations in individual clones. These observations suppose that frequencies of tumour reversions are a constant genetic characteristic of every cell line.