Combined with absence of p16/Arf tumor suppressors, the level of H-rasG12V may thus control key factors determining differentiation (Brn2, Mitf), EMT (JNK, Smad3, TGFβ signaling) and Ccl2 production (MAPK, JNK) during melanoma development as discussed hereafter. The gene discussed is SMAD3; the disease is neoplasm.