TY - JOUR
T1 - The function of melanotransferrin
T2 - A role in melanoma cell proliferation and tumorigenesis
AU - Dunn, L. L.
AU - Sekyer, E. O.
AU - Suryo Rahmanto, Y.
AU - Richardson, D. R.
N1 - Funding Information:
Dr David Lovejoy, Dr Ralph Watts and Miss Danuta Kalinowski of the Iron Metabolism and Chelation Program are thanked for their kind help in reviewing the paper before submission. We thank veterinary pathologists Dr J. Schuh (Applied Veterinary Pathobiology, Bainbridge Island, WA), Dr John W. Finney (Institute of Medical and Veterinary Science, Adelaide, South Australia) and Dr Terry Rothwell (Rothwell Consulting, Sydney, Australia) for their careful examination of tissue section histology. For assistance with the interpretation of statistical data from Affymetrix gene arrays, we kindly acknowledge Dr Mervyn Thomas (Emphron Informatics, Brisbane, Australia) for his tremendous assistance. Children’s Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children’s Hospital. This project was supported by a fellowship and project grants from the National Health and Medical Research Council of Australia.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - 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 the MTf-/- mice demonstrated no differences compared with 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 with MTf+/+ littermates. Considering the role of MTf in melanoma cells, PTGS was used to downregulate 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 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.
AB - 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 the MTf-/- mice demonstrated no differences compared with 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 with MTf+/+ littermates. Considering the role of MTf in melanoma cells, PTGS was used to downregulate 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 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.
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U2 - 10.1093/carcin/bgl045
DO - 10.1093/carcin/bgl045
M3 - Article
C2 - 16704991
AN - SCOPUS:33750429650
SN - 0143-3334
VL - 27
SP - 2157
EP - 2169
JO - Carcinogenesis
JF - Carcinogenesis
IS - 11
ER -