Functional role of MIA in melanocytes and early development of melanoma
Functional role of MIA in melanocytes and early development of melanoma
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DOI：
10.1038/sj.onc.1207797
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发表时间：
2004-08-12
期刊：
影响因子：
8
通讯作者：
Bosserhoff, AK
中科院分区：
文献类型：
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作者：
Poser, I;Tatzel, J;Bosserhoff, AK
蛋白质MIA（黑色素瘤抑制活性）在恶性黑色素瘤中高度表达，但在黑色素细胞中不表达。此外，MIA的表达与体内肿瘤进展相关。在此，研究了在人黑素瘤细胞系HMB 2中长期抑制MIA表达后MIA依赖性的基因表达变化。首先，我们观察到细胞形态的特征性变化，并发现在单层培养中生长的MIA缺陷细胞克隆中重新建立的细胞-细胞接触。实时逆转录-聚合酶链反应（RT-PCR）显示MIA缺陷细胞克隆中N-钙粘蛋白表达下调，E-钙粘蛋白表达恢复。此外，癌症cDNA阵列和蛋白质阵列都证实了MIA缺陷型黑素瘤细胞中几种其他黑素瘤相关基因（例如膜1型基质金属蛋白酶组织型纤溶酶原激活剂整合素β 3，分泌的酸性蛋白质，富含半胱氨酸和纤连蛋白）的显著下调，这通过实时RT-PCR和蛋白质印迹法证实。由于所有这些分子都与迁移相关，因此分析了MIA对人原代黑素细胞迁移的影响。在MIA的存在下，我们观察到黑素细胞的迁移能力增强，黑色素瘤相关基因的诱导以及由于失巢凋亡的细胞凋亡的抑制。这些结果表明，MIA的表达通过诱导进一步的黑素瘤相关基因促进黑素瘤进展。
The protein MIA(melanoma inhibitory activity) is highly expressed in malignant melanomas but not in melanocytes. Furthermore, expression of MIA correlates with tumor progression in vivo. Here, MIA-dependent changes of gene expression after long-term inhibition of MIA expression in the human melanoma cell line HMB2 were investigated. Primarily, we observed characteristic changes in cell morphology, and also found re-established cell-cell contacts in MIA-deficient cell clones grown in monolayer culture. Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed a downregulation of N-cadherin expression and a reinduction of E-cadherin expression in the MIA-deficient cell clones. Further, both cancer cDNA array and protein arrays verified a marked downregulation of several other melanoma-associated genes (e.g. membrane-type 1 matrix metalloproteinase tissue-type plasminogen activator integrin beta3, secreted protein acidic and rich in cysteins and fibronectin) in the MIA-deficient melanoma cells, confirmed by real-time RT-PCR and Western blotting. As all these molecules are associated with migration, the effect of MIA on migration of human primary melanocytes was analysed. In the presence of MIA, we observed enhanced migratory ability of melanocytic cells, induction of melanoma-associated genes as well as inhibition of apoptosis due to anoikis. These results suggest that expression of MIA promotes melanoma progression by inducing further melanoma-associated genes.