TY - JOUR
T1 - IL-4-induced Stat6 activities affect apoptosis and gene expression in breast cancer cells
AU - Zhang, Wen Jie
AU - Li, Ben Hui
AU - Yang, Xian Zi
AU - Li, Pin Dong
AU - Yuan, Qin
AU - Liu, Xiao Hong
AU - Xu, Shuang Bing
AU - Zhang, Yan
AU - Yuan, Jia
AU - Gerhard, Glenn S.
AU - Masker, Kathryn K.
AU - Dong, Cheng
AU - Koltun, Walter A.
AU - Chorney, Michael J.
N1 - Funding Information:
We wish to thank Maggie Slattery for help in cell culture, and Dr. Qing He Meng for assistance in RNA extraction. This work was supported by a grant to W.J. Zhang from the National Natural Science Foundation of China (NSFC No. 30470981).
PY - 2008/4
Y1 - 2008/4
N2 - 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 Stat6high phenotype and BT-20 being defective Stat6null phenotype, respectively. Breast cancer cells carrying Stat6null phenotype exhibited increased spontaneous apoptosis compared with those carrying Stat6high 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 Stat6null BT-20 cells and 23 genes unique to Stat6high ZR-75-1 cells, respectively. Furthermore, Stat6high and Stat6null 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.
AB - 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 Stat6high phenotype and BT-20 being defective Stat6null phenotype, respectively. Breast cancer cells carrying Stat6null phenotype exhibited increased spontaneous apoptosis compared with those carrying Stat6high 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 Stat6null BT-20 cells and 23 genes unique to Stat6high ZR-75-1 cells, respectively. Furthermore, Stat6high and Stat6null 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.
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U2 - 10.1016/j.cyto.2008.01.016
DO - 10.1016/j.cyto.2008.01.016
M3 - Article
C2 - 18342537
AN - SCOPUS:41149124798
SN - 1043-4666
VL - 42
SP - 39
EP - 47
JO - Cytokine
JF - Cytokine
IS - 1
ER -