The function of melanotransferrin: a role in melanoma cell proliferation and tumorigenesis
The function of melanotransferrin: a role in melanoma cell proliferation and tumorigenesis
复制标题
DOI：
10.1093/carcin/bgl045
复制
发表时间：
2006-11-01
期刊：
影响因子：
4.7
通讯作者：
Richardson, D. R.
中科院分区：
文献类型：
--
作者：
Dunn, L. L.;Sekyere, E. O.;Richardson, D. R.
黑素转铁蛋白(MTF)又称黑色素瘤抗原p97，是一种铁(Fe)结合转铁蛋白同源物，在黑色素瘤中高表达，在正常组织中低水平表达。已有研究表明MTF参与了铁代谢和细胞分化等多种过程。考虑到铁在许多代谢途径中的关键作用，例如DNA合成，了解MTF的功能是很重要的。为了确定MTF的作用，建立了两个模型：(I)MTF基因敲除(MTF-/-)小鼠和(Ii)通过转录后基因沉默(PTGS)下调MTF在黑色素瘤细胞中的表达。对MTF-/-小鼠的检测表明，与野生型窝种相比没有差异。然而，基因芯片分析显示，与MTF+/+小鼠相比，Mef2a、TCF4、GLS和APOD等与增殖相关的分子在MTF-/-小鼠中的表达存在差异。考虑到MTF在黑色素瘤细胞中的作用，PTGS被用来分别下调>；90和>；80%的MTF mRNA和蛋白水平。这导致了对扩散和迁移的抑制。在MTF-/-小鼠中发现，在MTF表达抑制的黑色素瘤细胞中，hMEF2A和hTCF4与亲本细胞相比上调。此外，当MTF表达降低的黑色素瘤细胞注射到裸鼠体内时，肿瘤生长明显减少，这表明MTF在增殖和肿瘤发生中起作用。
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.