Epidermal growth factor inhibits transiently the progression from G2-phase to mitosis: a receptor-mediated phenomenon...

An immediate effect of epidermal growth factor (EGF) on the cell cycle is described. EGF, when given to replicating cells such as HeLa, A431, and D HER 14, very rapidly inhibits the transition from G2 phase to mitosis (M) in a transient fashion. The influence of EGF (10(-10) to 10(-7) M concentrations) on the G2-M transition of individual cells has been analyzed by time-lapse photography in cell lines carrying intact, mutated, or no EGF receptor. The G2-M transition of cells devoid of EGF receptor or carrying an EGF receptor devoid of most of the cytoplasmic domain was not influenced by EGF. In cells carrying intact EGF receptor, EGF caused a transient and dose-dependent delay in G2 phase which could last for greater than 2 h. Cells were inhibited in G2 within less than 10-20 min prior to prophase. A parasynchronous recovery from G2 inhibition was observed at large EGF concentrations; the G2-M transition rate exceeded that of the controls. The system described may represent a model for the mechanistic analysis of a ligand-induced transient restriction of the cell cycle, particularly at the G2-M border.