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

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 Stat6^high (40% vs 12%). Expression analyses showed that IL-4 upregulated 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 Stat6 pathway, suggesting Stat6^null cells 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 Stat6^high cells, respectively. Furthermore, Stat6^null and Stat6^high cells 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.