STAT6 mediates interleukin-4 growth inhibition in human breast cancer cells
STAT6 mediates interleukin-4 growth inhibition in human breast cancer cells
复制标题
DOI：
10.1038/sj.neo.7900248
复制
发表时间：
2002-07-01
期刊：
影响因子：
4.8
通讯作者：
Yee, D
中科院分区：
文献类型：
--
作者：
Gooch, JL;Christy, B;Yee, D
除了作为造血生长因子外，白细胞介素 4 (IL-4) 还可在体外和体内抑制某些转化细胞的生长。在这项研究中，我们发现在 MCF-7 乳腺癌细胞中，胰岛素受体底物 (IRS)-1、IRS-2 以及信号转导子和转录激活子 6 (STAT6) 在 IL-4 处理后发生磷酸化。 IL-4 处理可增强 STAT6 DNA 结合。即使 IRS-1 耗尽后，STAT6 也会激活，表明这两条途径是独立的。为了检查 STAT6 在 IL-4 介导的生长抑制和细胞凋亡中的作用，将全长 STAT6 cDNA 转染至 MCF-7 细胞中。 STAT6 的瞬时过表达导致该蛋白在细胞质和核中表达，增加了对 IL-4 的 DNA 结合响应，并增加了 IL-4 响应启动子的反式激活。在STAT6转染的细胞中，基础增殖减少，而细胞凋亡增加。最后，与单独载体转染的细胞相比，STAT6 的稳定表达导致病灶形成减少。这些结果表明 STAT6 是 IL-4 介导的人乳腺癌细胞生长抑制和细胞凋亡诱导所必需的。
In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4) inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS)-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6) are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a full-length STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector - transfected cells alone. These results suggest STAT6 is required for IL-4-mediated growth inhibition and induction of apoptosis in human breast cancer cells.