不同Stat6表型乳腺癌细胞IL-4/Stat6信号通路调节基因表达的研究

Gene expression regulated by IL-4/Stat6 signaling pathway in breast cancer cells with different Stat6 activation phenotypes

目的:探讨不同乳腺癌细胞株Stat6活化分型的可行性及IL-4的作用机制。方法:流式细胞仪测定不同Stat6表型细胞株ZR-75-1和BT-20的早期凋亡率;应用Affymetrix基因芯片测定IL-4刺激前后的基因表达谱变化。结果:Stat6null表型细胞与Stat6high相比早期凋亡增加(40%vs12%);在Stat6null细胞株有2193个基因/转录产物表达升高,而Stat6high细胞株中2600个基因/转录产物表达升高,且Stat6high细胞和Stat6null细胞中与凋亡和转移相关的基因表达谱明显不同;但不论在Stat6high还是Stat6null细胞株,IL-4均上调CCL26、SOCS1、CISH、EGLN3和SIDT1基因,而下调DUSP1、FOS和FOSB基因。结论:在乳腺癌细胞中,IL-4可能像在免疫细胞中一样,通过Stat6或非Stat6途径而发挥功能。

OBJECTIVE： To investigate the feasibility of different phenotype of Stat6 activity in different breast cancer lines and the mechanism of IL-4. METHODS： To analyz the early apoptosis of ZR-75-1 and BT 20 by flow cytometry and constitutive expression profile by Affymetrix Human Genome U133 Plus 2.0 Array GeneChips whether being treated by IL-4 or not. RESULTS： Cells carrying defective Stat6^null phenotype exhibited increased spontaneous apoptosis versus those carrying Slat6high （40% vs 12%）. Expression analyses showed that IL-4 up- regulated CCL26, SOCS1, CISH, EGLN3, and SIDT1, and down-regulated DUSP1, FOS and FOSB, respectively, common to both Stat6^high and Stat6^null cells. CCL26 and SOCS1 were known to be regulated by IL-4 via Star6 pathway, suggesting Stat6^unll ceils having residual functions. Analyses of constitutive expression revealed 2 193 genes/transcripts overexpressed in Stat6^null cells, and vice verse, 2 600 genes/transcripts overexpressed in Stat^6high ceils, respectively. Furthermore, Stat6^null and Stat6^high ceils had very different profiles of constitutively expressed genes relevant to apoptosis and metastasis, amongst others. CONCLUSION： These observations suggest that, like in immune cells, IL-4 may function via Stat6-dependent and -independent pathways in breast cancer cells.