Stat3 as an oncogene
Stat3 as an oncogene
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DOI：
10.1016/s0092-8674(00)81959-5
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发表时间：
1999-08-06
期刊：
影响因子：
64.5
通讯作者：
Darnell, JE
中科院分区：
文献类型：
--
作者：
Bromberg, JF;Wrzeszczynska, MH;Darnell, JE
STAT是介导细胞因子和生长因子指导的转录的潜在转录因子。在许多人类癌症和转化细胞系中，Stat 3被持续激活，并且在细胞培养中，活性Stat 3是转化所需的，增强转化或阻断细胞凋亡。我们报告说，两个半胱氨酸残基内的C-末端环的SH 2结构域的Stat 3的取代产生一个分子，自发二聚化，结合到DNA，并激活转录。永生化成纤维细胞中的Stat 3-C分子引起细胞转化，通过软琼脂中的集落形成和裸鼠中的肿瘤形成来评分。因此，活化的Stat 3分子本身可以介导细胞转化，并且实验将注意力集中在组成性Stat 3活化在人类肿瘤中的重要性上。
STATs are latent transcription factors that mediate cytokine- and growth factor-directed transcription. In many human cancers and transformed cell lines, Stat3 is persistently activated, and in cell culture, active Stat3 is either required for transformation, enhances transformation, or blocks apoptosis. We report that substitution of two cysteine residues within the C-terminal loop of the SH2 domain of Stat3 produces a molecule that dimerizes spontaneously, binds to DNA, and activates transcription. The Stat3-C molecule in immortalized fibroblasts causes cellular transformation scored by colony formation in soft agar and tumor formation in nude mice. Thus, the activated Stat3 molecule by itself can mediate cellular transformation and the experiments focus attention on the importance of constitutive Stat3 activation in human tumors.