SMAD4 and neoplasm: The expression of hepcidin mRNA is generally inhibited in HCC, which is obvious in cancerous tissues but not in noncancerous tissues and has nothing to do with the degree of tumor differentiation, the tumor stage, or tumor recurrence.[89] The HAMP promoter that controls the expression of the HAMP gene, which encodes hepcidin, contains binding motifs for C/EBP,[90] hepatocyte nuclear factor 4,[90] STAT-3,[91] and SMAD4.[92] Weizer-Stern et al[93] have shown that the promoter region of the HAMP gene contains a presumed p53 response element, and its expression is caused by the activation of p53.