ERβ and PEA3 co-activate IL-8 expression and promote the invasion of breast cancer cells

Metastasis represents the major remaining cause of mortality in human breast cancer. Interleukin-8 (IL-8), a proinflammatory chemokine, plays an important role during tumor angiogenesis and metastasis. In this study, we found that IL-8 and ERbeta (ER beta) showed positive association. Overexpression of ER beta or PEA 3 could upregulate IL-8 promoter activity, mRNA and secretion; silencing of ER beta or PEA 3 decreased IL-8 mRNA and secretion. ER beta and PEA 3 increased IL-8 expression through binding to the IL-8 promoter and increased cell invasion. HER2 could increase ER beta and PEA 3 expression and their binding to the IL-8 promoter. We conclude that ER beta and PEA 3 play important roles in tumor invasion by regulating IL-8 expression, and HER2 maybe the upstream of ER beta and PEA3-IL-8 pathway.