C-myc Protein Expression in Untransformed Fibroblasts

We have examined and quantitated the expression of c-myc protein in two untransformed fibroblast cell lines, murine Swiss 3T3 and human MRC-5, c-myc protein is not detectable in quiescent cells, but it is rapidly induced upon mitogenic stimulation. Peak expression is seen about 3-5 h after serum stimulation, and corresponds to about 3-6000 molecules per cell (mpc). Thereafter, levels fall back to a quiescent level in confluent fibroblasts, but remain elevated at 1-3000 mpc in subconfluent cells. The c-myc protein is phosphorylated and has the same size and short half-life as seen in tumour cells. Removal of serum growth factors from the culture medium causes very rapid loss of the c-myc protein from all cells, irrespective of their positions in the cell cycle. Thus, c-myc expression is continuously dependent upon the presence of mitogens. However, no single tested mitogen is obligatory for maintenance of expression in proliferating cells. Growth arrest of cells, either by metabolite starvation or by drugs which inhibit DNA synthesis, does not affect expression of the c-myc protein, which remains completely dependent upon the presence of mitogens. These data are consistent with the c-myc protein's having a continuous role in proliferating cells as an intracellular integrator of growth regulatory signalling pathways.