Although it was confirmed that modulation of RasGRP3 contributes to Akt and ERK1/2 activation in prostate cancer and melanoma cells [12,13], here we are the first to demonstrate that RasGRP3 contributed to signaling downstream of IGF-I and EGF in the MCF7 and T-47D cells by modifying the level of IGF-I and EGF induced phosphorylation of Akt and ERK 1/2. The gene discussed is EGF; the disease is melanoma.