IL-4-induced Stat6 activities affect apoptosis and gene expression in breast cancer cells
IL-4-induced Stat6 activities affect apoptosis and gene expression in breast cancer cells
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DOI：
10.1016/j.cyto.2008.01.016
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发表时间：
2008-04-01
期刊：
影响因子：
3.8
通讯作者：
Chorney, Michael J.
中科院分区：
文献类型：
--
作者：
Zhang, Wen Jie;Li, Ben Hui;Chorney, Michael J.
IL-4 诱导的 Stat6 信号传导在多种细胞类型中活跃，包括免疫细胞和癌细胞，并在基因表达调控中发挥重要作用。使用 EMSA 凝胶位移测定和 Stat6 抗体，我们对两种乳腺癌细胞系进行了表型分析，ZR-75-1 是活跃的 Stat6（高）表型，BT-20 是有缺陷的 Stat6（无效）表型。与携带 Stat6(high) 表型的乳腺癌细胞相比，携带 Stat6(null) 表型的乳腺癌细胞表现出自发性凋亡增加。表达微阵列分析表明，在这些乳腺癌细胞中，IL-4 分别上调 CCL26、SOCS1、CISH、EGLN3 和 SIDT1，并下调 DUSP1、FOS 和 FOSB。其中，CCL26和SOCS1是已知的受IL-4/Stat6通路调节的基因，而CISH、EGLN3、SIDT1、DUSP1、FOS和FOSB是首次被证明对IL-4有反应的新基因。 IL-4 还分别上调了 Stat6(null) BT-20 细胞特有的 38 个基因和 Stat6(high) ZR-75-1 细胞特有的 23 个基因。此外，Stat6（高）和Stat6（无效）细胞显示出与细胞凋亡和转移等相关的组成型表达基因的非常不同的谱，这可以作为有价值的表达数据库并为乳腺癌中IL-4/Stat6通路的详细研究提供依据。 (c) 2008 Elsevier Ltd. 保留所有权利。
IL-4-induced Stat6 signaling is active in a variety of cell types, including immune cells and cancer cells, and plays an important role in the regulation of gene expression. Using EMSA gel shift assay and an antibody to Stat6, we phenotyped two breast cancer cell lines, ZR-75-1 being active Stat6(high) phenotype and BT-20 being defective Stat6(null) phenotype, respectively. Breast cancer cells carrying Stat6(null) phenotype exhibited increased spontaneous apoptosis compared with those carrying Stat6(high) phenotype. Expression microarray analyses demonstrated that IL-4 upregulated CCL26, SOCS1, CISH, EGLN3, and SIDT1, and downregulated DUSP1, FOS, and FOSB, respectively, in these breast cancer cells. Among those genes, CCL26 and SOCS1 were known genes regulated by IL-4/Stat6 pathway, but CISH, EGLN3, SIDT1, DUSP1, FOS, and FOSB were novel genes demonstrated to be IL-4 responsive for the first time. IL-4 also upregulated 38 genes unique to Stat6(null) BT-20 cells and 23 genes unique to Stat6(high) ZR-75-1 cells, respectively. Furthermore, Stat6(high) and Stat6(null) cells showed very different profiles of constitutively expressed genes relevant to apoptosis and metastasis among others, which serve as a valuable expression database and warrant for detailed studies of IL-4/Stat6 pathway in breast cancer. (c) 2008 Elsevier Ltd. All rights reserved.