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Melanotransferrin (MTf) or melanoma tumor antigen p97 is an iron (Fe) binding transferrin homolog expressed highly on melanomas and at lower levels on normal tissues. It has been suggested that MTf is involved in a variety of processes such as Fe metabolism and cellular differentiation. Considering the crucial role of Fe in many metabolic pathways, for example, DNA synthesis, it is important to understand the function of MTf. To define the roles of MTf, two models were developed: (i) an MTf knockout (MTf  −/−) mouse and (ii) downregulation of MTf expression in melanoma cells by post-transcriptional gene silencing (PTGS). Examination of theMTf  −/−mice demonstrated no differences compared with wild-type littermates. However, microarray analysis showed differential expression of molecules involved in proliferation such asMef2a, Tcf4, GlsandApodinMTf  −/−mice compared withMTf  +/+littermates. Considering the role of MTf in melanoma cells, PTGS was used to downregulateMTfmRNA and protein levels by &gt;90 and &gt;80%, respectively. This resulted in inhibition of proliferation and migration. As found inMTf  −/−mice, in melanoma cells with suppressed MTf expression,hMEF2AandhTCF4were upregulated compared with parental cells. Furthermore, when melanoma cells with decreased MTf expression were injected into nude mice, tumor growth was markedly reduced, suggesting a role for MTf in proliferation and tumorigenesis.

The function of melanotransferrin: a role in melanoma cell proliferation and tumorigenesis