We found that p53 tumor suppressor gene is the key gene that is involved in the signal transduction of the epidermal growth factor (EGF). In this study, we investigated apoptosis induced by high concentration of EGF and modulation of cell cycle progression by high concentration of EGF in breast and esophageal cancer cells transplanted into nude mice. In situ apoptosis detection was performed using Apop Tag(TM) in situ apoptosis detection kit peroxidase. DNA fragmentation analysis was also performed to detect apoptosis. Modulation of cell cycle progression was detected through PCNA immunostaining. Two mu g of EGF induced apoptosis in ES-4 esophageal cancer cells and MX-1 breast cancer cells after increased accumulation of p53 induced by 2 mu g of EGF. At the same time, there was negative PCNA immunostaining in these cells. On the other hand, using UM-1 breast cancer cells, we inhibited p53 expression by 2 mu g of TGF-beta 1 and detected apoptosis and PCNA immunostaining. We detected no apoptosis, however, strong positive PCNA immunostaining was detected in these cells. The evidence demonstrates that high concentration of EGF induces apoptosis in MX-1 human breast cancer and ES-4 human esophageal cancer transplanted into nude mice and indicates that there is a signal pathway of EGF that induces apoptosis.