AEBP1 ALTERS MATRIX SIGNALLING AND IS RESPONSIVE TO INFLAMMATION IN THE MAMMARY GLAND

Abstract

Breast cancer is characterized in part by chronic inflammation and tissue remodelling in the mammary gland. Adipocyte enhancer binding protein 1 (AEBP1), a pro-inflammatory protein, is up-regulated in breast cancer and enhances cytokine secretion in the mammary tumour microenvironment. AEBP1 over-expression in cultured macrophages resulted in increased enzymatic activity of MMP-9, a matrix metalloproteinase implicated in processing cytokines and stimulating tumour cell growth and mobility. MMP-9 activates the cytokine tumour necrosis factor-alpha (TNF?), and is required for the transformation of epithelial cells by the cytokine interleukin 6 (IL6). Treatment of epithelial cells with TNF? and IL6, both of which promote tumourigenesis, induced AEBP1 expression. Chromatin immunoprecipitation results suggested AEBP1 induction is directly mediated by pro-inflammatory transcription factors NF-?B and STAT3, downstream effectors of TNF? and IL6, respectively. AEBP1 induction may enhance inflammation, thereby contributing to cell proliferation and survival.