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Melanotransferrin (melanoma tumour antigen p97) is an§iron-§binding transferrin homologue expressed at high§levels on §melanoma tumours and at lower levels on normal§tissues. Unlike its §relatives, transferrin and lactoferrin,§melanotransferrin is §membrane-bound. These properties suggest that§melanotransferrin §may assist melanoma and other tumour cell types with§their increased requirement for iron. To address this§hypothesis we §utilised models including: (i) the melanotransferrin§knockout mouse, and (ii) systematic down-regulation of §melanotransferrin in melanoma cells using siRNA.§Rigorous §phenotypic§characterisation of this knockout mouse demonstrated no §differences in iron metabolism, behaviour or other§physiological parameters compared to wild-type§controls. In §melanoma cells, melanotransferrin was found to§facilitate §proliferation and §migration, and also to enhance tumourigenesis in nude§mice. §Moreover, whole genome array analysis of these models§in addition §to cell models of melanotransferrin over-expression§indicated §differences in genes associated with growth.
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