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 Stat6null phenotype exhibited increased spontaneous apoptosis versus those carrying Stat6high(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 Stat6high and Stat6null cells.CCL26 and SOCS1 were known to be regulated by IL-4 via Stat6 pathway,suggesting Stat6null cells having residual functions.Analyses of constitutive expression revealed 2 193 genes/transcripts overexpressed in Stat6null cells,and vice verse,2 600 genes/transcripts overexpressed in Stat6high cells,respectively.Furthermore,Stat6null and Stat6high 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.