Inhibition of constitutively activated Stat3 correlates with altered Bcl-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells
Inhibition of constitutively activated Stat3 correlates with altered Bcl-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells
复制标题
DOI：
10.1038/sj.leu.2401415
复制
发表时间：
1999-05-01
期刊：
影响因子：
11.4
通讯作者：
Odum, N
中科院分区：
文献类型：
--
作者：
Nielsen, M;Kæstel, CG;Odum, N
Jak/Stat信号通路将来自许多细胞因子和生长因子受体的信号传递到细胞核中的靶基因。最近在许多肿瘤细胞中观察到Stat 3的组成性激活，并且已经提出Stat 3信号通路的失调与恶性转化有关。在先前的研究中，我们发现蕈样肉芽肿肿瘤细胞中存在组成性酪氨酸磷酸化的Stat 3。在这里，我们表明，Jak激酶抑制剂，Ag 490，抑制Stat 3的组成性结合的寡核苷酸代表的STAT结合序列从ICAM启动子。Stat 3结合DNA的能力降低先于抗凋亡Bcl-2和促凋亡Bax蛋白表达的动态改变（Bcl-2表达降低和Bax表达增加）和凋亡诱导。因此，我们的数据表明，Stat 3参与致癌转化可能是通过调节生存信号介导的。
The Jak/Stat signaling pathway transmits signals from many cytokine and growth factor receptors to target genes in the nucleus. Constitutive activation of Stat3 has recently been observed in many tumor cells and dysregulation of the Stat signaling pathway has been proposed to be implicated in malignant transformation. In a previous study, we found constitutively tyrosine phosphorylated Stat3 in mycosis fungoides tumor cells. Here, we show that the Jak kinase inhibitor, Ag490, inhibits the constitutive binding of Stat3 to an oligonucleotide representing the Stat-binding sequence from the ICAM promotor. The decreased ability of Stat3 to bind DNA precedes dynamic alterations in the expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins (decreased Bcl-2 expression and increased Bax expression) and induction of apoptosis. Thus, our data suggest that the involvement of Stat3 in oncogenic transformation could be mediated through regulation of survival signals.