Macrophage Inhibitory Cytokine-1 Is Overexpressed in Malignant Melanoma and Is Associated with Tumorigenicity
Macrophage Inhibitory Cytokine-1 Is Overexpressed in Malignant Melanoma and Is Associated with Tumorigenicity
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DOI：
10.1038/jid.2008.270
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发表时间：
2009-02-01
影响因子：
6.5
通讯作者：
Parsons, Peter G.
中科院分区：
文献类型：
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作者：
Boyle, Glen M.;Pedley, Julie;Parsons, Peter G.
在过去的四十年里，恶性黑色素瘤的发病率急剧上升。转移性黑色素瘤与预后差有关，因为目前的治疗对延长生存期或降低死亡率没有显著影响。我们已经确定了转化生长因子- β超家族的一个成员，巨噬细胞抑制细胞因子(MIC)-1，它在黑色素瘤细胞中高度表达。通过western blot分析检测了53种黑色素瘤细胞系中MIC-1的相对表达，其中35种（66%）的MIC-1水平明显高于正常黑色素细胞。原发性黑色素瘤活检（22例中的15例）通过免疫组织化学检测发现含有表达低水平MIC-1的细胞。相比之下，所有转移性黑色素瘤活检检查（16 / 16）均有MIC-1的强烈表达。MIC-1的表达依赖于有丝分裂原激活的蛋白激酶途径，并且是小眼相关转录因子的转录靶点。在三种黑色素瘤细胞系中，使用稳定的短发夹RNA敲除MIC-1的表达，可显著降低其致瘤性(P
The incidence of malignant melanoma has increased dramatically over the past four decades. Metastatic melanoma is associated with poor prognosis, as the current treatments do not have a significant impact on prolonging survival or decreasing mortality. We have identified a member of the transforming growth factor-beta superfamily, macrophage inhibitory cytokine (MIC)-1, which is highly expressed in melanoma cells. Of 53 melanoma cell lines that were examined for relative MIC-1 expression by western blot analysis, 35 (66%) showed significantly higher levels of MIC-1 compared to normal melanocytes. Primary melanoma biopsies (15 of 22) were found to contain cells expressing low levels of MIC-1 as determined by immunohistochemistry. In contrast, all metastatic melanoma biopsies examined (16 of 16) had strong expression of MIC-1. Expression of MIC-1 was found to be dependent on the mitogen-activated protein kinase pathway, and is a transcriptional target of the microphthalmia-associated transcription factor. Knockdown of MIC-1 expression using stable short-hairpin RNA in three melanoma cell lines showed a significant decrease in tumorigenicity (P