Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8

The IL-8 promoter is repressed by DACH1 requiring the DS domain. (A) IL-8 mRNA abundance was determined by QT-PCR in MCF10A-Ras or MDA-MB-231 cells expressing DACH1. In MDA-MB-231 cells, TNF-α was used to induce IL-8 production. (B and C) Schematic representation of DACH1 expression vectors and mutants, IL-8 promoter and point mutant luciferase reporter gene contractions. The effect of DACH1 on IL-8 promoter activity is shown normalized to Renilla Luciferase activity as an internal control. Data are mean ± SEM of n > 5 separate experiments. (D) ChIP analysis of DACH1 recruitment to either the endogenous IL-8 promoter in MDA-MB-231 cells (above) or to transfected IL-8 promoter constructions encoding either the WT, AP-1, or NFκB point mutants of the IL-8 promoter in HEK293 cells. Each experiment was conducted on at least two separate occasions with the FLAG antibody and was also conducted by using an antibody directed to DACH1 with similar results. Quantitative data of relative abundance of DACH1 recruitment to the IL-8 promoter is shown as mean data. *, P < 0.01.