Louise Dunn

Melanotransferrin: Examination of the Functional Role of Melanoma Tumour Antigen P97 Louise Dunn

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.