Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics
Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics
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DOI：
10.1038/ng0996-50
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发表时间：
1996-09-01
期刊：
影响因子：
30.8
通讯作者：
Urabe, K
中科院分区：
文献类型：
--
作者：
Tachibana, M;Takeda, K;Urabe, K
微小眼炎相关转录因子(MITF)编码一种带有碱性螺旋环螺旋拉链(bHLH-Zip)基序的转录因子。MITF突变发生在2型瓦登堡综合征患者中，这是一种与黑素细胞异常相关的疾病。在这里，我们发现MITF的异位表达可以将NIH/3T3成纤维细胞转化为具有黑素细胞特征的细胞。MITF转基因细胞形成形态改变的细胞灶，类似于癌基因诱导的细胞，但没有表现出恶性表型。相反，它们含有树突状细胞，表达酪氨酸酶和酪氨酸酶相关蛋白1等黑素生成标志蛋白。大多数MITF转基因克隆细胞具有树突状细胞形态并表达黑素生成标记物，但在转导密切相关TFE3基因的细胞中未观察到这种特性。我们的发现表明，MITF在黑素细胞分化过程中起着至关重要的作用。
MITF (microphthalmia-associated transcription factor) encodes a transcription factor with a basic-helix-loop-helix-zipper (bHLH-Zip) motif. MITF mutations occur in patients with Waardenburg syndrome type 2, a disorder associated with melanocyte abnormalities. Here we show that ectopic expression of MITF converts NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci of morphologically altered cells, which resemble those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase-related protein 1. Most cloned cells of MITF transfectants exhibited dendritic morphology and expressed melanogenic markers, but such properties were not observed in cells transfected with closely related TFE3 cDNA. Our findings indicate that MITF is critically involved in melanocyte differentiation.