The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma.
The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma.
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DOI：
10.1038/sj.bjc.6601212
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发表时间：
2003-09-15
影响因子：
8.8
通讯作者：
Lee, K A W
中科院分区：
文献类型：
--
作者：
Li, K K C;Goodall, J;Goding, C R;Liao, S-K;Wang, C-H;Lin, Y-C;Hiraga, H;Nojima, T;Nagashima, K;Schaefer, K-L;Lee, K A W
透明细胞肉瘤（CCS）与EWS/ATF1癌基因相关，EWS/ATF1癌基因是由尤因肉瘤癌基因（EWS）和细胞转录因子ATF1的染色体融合产生的。CCS的黑素细胞特征表明，作为黑素细胞分化的主要诱导剂，小眼相关转录因子（Mitf）可能在CCS中缺失表达。因此，我们发现在几种培养的CCS细胞系（Su-ccs-1、DTC1、Kao、MST-1、MST-2和MST-3）中存在黑色素细胞特异性Mitf亚型（Mitf- m）的mRNA和蛋白。因此，上述细胞系为研究Mitf-M在CCS和黑素细胞分化中的作用提供了宝贵的实验资源。Mitf-M的黑色素细胞特异性表达是通过Mitf-M启动子中atf依赖的黑色素细胞特异性camp反应元件实现的，而CCS细胞中Mitf-M的表达表明，EWS/ATF1（一种强而混杂的camp诱导启动子激活剂）可能激活Mitf-M启动子。然而，令人惊讶的是，在使用CCS细胞、黑素细胞或非黑素细胞的瞬态试验中，Mitf-M启动子没有被EWS/ATF1激活。因此，我们的研究结果表明，在CCS细胞中，Mitf-M启动子的激活可能需要适当的染色体背景，或者Mitf-M启动子不直接被EWS/ATF1激活。
Clear cell sarcoma (CCS) is associated with the EWS/ATF1 oncogene that is created by chromosomal fusion of the Ewings Sarcoma oncogene (EWS) and the cellular transcription factor ATF1. The melanocytic character of CCS suggests that the microphthalmia-associated transcription factor (Mitf), a major inducer of melanocytic differentiation, may be miss-expressed in CCS. Accordingly, we show that the mRNA and protein of the melanocyte-specific isoform of Mitf (Mitf-M) are present in several cultured CCS cell lines (Su-ccs-1, DTC1, Kao, MST-1, MST-2 and MST-3). The above cell lines thus provide a valuable experimental resource for examining the role of Mitf-M in both CCS and melanocyte differentiation. Melanocyte-specific expression of Mitf-M is achieved via an ATF-dependent melanocyte-specific cAMP-response element in the Mitf-M promoter, and expression of Mitf-M in CCS cells suggests that EWS/ATF1 (a potent and promiscuous activator of cAMP-inducible promoters) may activate the Mitf-M promoter. Surprisingly, however, the Mitf-M promoter is not activated by EWS/ATF1 in transient assays employing CCS cells, melanocytes or nonmelanocytic cells. Thus, our results indicate that Mitf-M promoter activation may require an appropriate chromosomal context in CCS cells or alternatively that the Mitf-M promoter is not directly activated by EWS/ATF1.