Carcinogenesis Advance Access published online on May 16, 2006
Carcinogenesis, doi:10.1093/carcin/bgl045
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1 Children's Cancer Institute Australia for Medical Research, Iron Metabolism and Chelation Program, PO Box 81, High St, Randwick, Sydney, New South Wales, 2031 Australia
* To whom correspondence should be addressed. 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 e.g., DNA synthesis, it is important to understand the function of MTf. To define the roles of MTf, two models were developed: (i) a MTf knockout (MTf-/-) mouse and (ii) down-regulation of MTf expression in melanoma cells by post-transcriptional gene silencing (PTGS). Examination of the MTf-/- mice demonstrated no differences compared to wild-type littermates. However, microarray analysis showed differential expression of molecules involved in proliferation such as Mef2a, Tcf4, Gls and Apod in MTf-/- mice compared to MTf+/+ littermates. Considering the role of MTf in melanoma cells, PTGS was used to down-regulate MTf mRNA and protein levels by >90% and >80%, respectively. This resulted in inhibition of proliferation and migration. As found in MTf-/- mice, in melanoma cells with suppressed MTf expression, hMEF2A and hTCF4, were up-regulated compared to 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.
Received January 20, 2006
Revised March 23, 2006
Accepted March 25, 2006
CANCER BIOLOGY
The function of melanotransferrin: a role in melanoma cell proliferation and tumorigenesis
L. L. Dunn 1 
,
E. O. Sekyere 1 ,
Y. Suryo Rahmanto 1,
and
D. R. Richardson 2 *
2 The Heart Research Institute, 145 Missenden Rd, Camperdown, Sydney, New South Wales, 2050 Australia
D. R. Richardson, E-mail: d.richardson{at}pathology.usyd.edu.au
Abstract These authors contributed equally to this manuscript.
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