Levels of c-myc oncogene mRNA are invariant throughout the cell cycle

Abstract

The steady-state messenger RNA levels of several genes increase when cells are stimulated to proliferate^1–4. The transcripts from one such gene, the proto-oncogene c-myc, increase approximately 20-fold shortly after cells are stimulated to proliferate and then decline before the onset of DNA synthesis^1,5. It has been inferred from these data that expression of c-myc may be specific to the G₁ portion of the cell cycle⁵. Alternatively, this transient increase in c-myc mRNA following the stimulation of quiescent cells could be the result of an activational event that renders the cells competent to enter the cell cycle. To distinguish between these possibilities, we performed experiments to determine whether the amount of c-myc mRNA fluctuates during the cell cycle in cells that are under constant stimulation to proliferate. Although c-myc mRNA does undergo a transient increase within 2 h of serum stimulation of quiescent serum-deprived cells, our results show that the level of c-myc mRNA is constant throughout the cell cycle and does not diminish in density-arrested cells maintained in the presence of serum growth factors. In contrast to c-myc, the mRNA levels of two other genes whose expression has been associated with cellular proliferation^6–8 do show consistent variations within the cell cycle. Both thymidine kinase (TK) and histone 2b (H2b) mRNA levels increase during S phase in continuously growing cells and decrease when cell replication ceases in density-arrested cultures. Therefore, the transient increase in c-myc transcription following the activation of quiescent cells is not due to the type of cell cycle-dependent regulation characteristic of the TK and H2b genes.