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

L. L. Dunn, E. O. Sekyer, Yohan Suryo Rahmanto, D. R. Richardson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2157-2169
Number of pages13
JournalCarcinogenesis
Volume27
Issue number11
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

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Melanoma
Carcinogenesis
Cell Proliferation
RNA Interference
Down-Regulation
Melanoma-Specific Antigens
Neoplasm Antigens
Microarray Analysis
Transferrin
Metabolic Networks and Pathways
Nude Mice
Knockout Mice
Iron
Messenger RNA
DNA
Growth
Mouse Mfi2 protein
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research

Cite this

Dunn, L. L., Sekyer, E. O., Suryo Rahmanto, Y., & Richardson, D. R. (2006). The function of melanotransferrin: A role in melanoma cell proliferation and tumorigenesis. Carcinogenesis, 27(11), 2157-2169. https://doi.org/10.1093/carcin/bgl045

The function of melanotransferrin : A role in melanoma cell proliferation and tumorigenesis. / Dunn, L. L.; Sekyer, E. O.; Suryo Rahmanto, Yohan; Richardson, D. R.

In: Carcinogenesis, Vol. 27, No. 11, 15.11.2006, p. 2157-2169.

Research output: Contribution to journalArticle

Dunn, LL, Sekyer, EO, Suryo Rahmanto, Y & Richardson, DR 2006, 'The function of melanotransferrin: A role in melanoma cell proliferation and tumorigenesis', Carcinogenesis, vol. 27, no. 11, pp. 2157-2169. https://doi.org/10.1093/carcin/bgl045
Dunn, L. L. ; Sekyer, E. O. ; Suryo Rahmanto, Yohan ; Richardson, D. R. / The function of melanotransferrin : A role in melanoma cell proliferation and tumorigenesis. In: Carcinogenesis. 2006 ; Vol. 27, No. 11. pp. 2157-2169.
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