Transcription of the c-myc oncogene is altered in spontaneously immortalized rodent fibroblasts.

Cellular immortalization seems generally to be a necessary, but not sufficient step in tumourigenesis. We have analysed the role of the cellular oncogene, c-myc in the process of in vitro cellular ageing and spontaneous cellular immortalization using rodent fibroblasts. The steady-state level of c-myc of mouse and rat fibroblasts does not change significantly during cellular ageing in vitro. By contrast, the steady state level of c-myc mRNA increases 3- to 20-fold upon spontaneous establishment of these rodent fibroblasts. The increase in the steady-state level of this mRNA is essentially due to an increase in the transcriptional rate. Not all oncogenes respond in this way; the mRNA levels of both c-fos and c-K-ras do not show the same alteration. The changes in the steady-state level of c-myc mRNA are not due to gene amplification nor to gross gene rearrangements or translocations. However, the response of the myc gene to growth factor stimulation is present apparently equally in both mortal and immortal cells; a difference is seen in an increased maintenance of high c-myc mRNA levels after growth stimulation in established cell lines. Both young and senescent mortal cells, as well as immortal cells, respond to mitogen stimulation with a sharp increase in c-myc mRNA levels. Thus, senescent cells are able to see mitogen signals, but do not go on to initiate DNA synthesis. We also demonstrated that the c-myc mRNA levels do not respond to serum concentration above a minimum level, nor do they respond to factors in the conditioned medium of immortal cell cultures.