Ectopic expression of the ErbB-3 binding protein Ebp1 inhibits growth and induces differentiation of human breast cancer cell lines

Abstract

Ebp1, an ErbB‐3 binding protein, translocates from the cytoplasm to the nucleus of human breast cancer cells after treatment with the ErbB‐3 ligand, heregulin. The purpose of these studies was to examine the effects of ectopic expression of ebp1 on the biological properties of human ErbB‐3–expressing breast carcinoma cell lines. Ectopic expression of ebp1 in ErbB‐2, ErbB‐3–expressing breast carcinoma cell lines resulted in inhibition of colony formation, a decreased proliferation rate, an accumulation of cells in the G2/M phase of the cell cycle, and suppression of growth in soft agar. Ectopic expression of ebp1 led to a more differentiated phenotype in AU565 breast cancer cells, as evidenced by increased expression of lipid droplets and of the milk protein casein. Basal phosphorylation of extracellular regulated kinases (Erks) 1 and 2, kinases activated by heregulin treatment, was also observed in ebp1 transfectants. The promoter for the intercellular adhesion molecule‐1 gene, a heregulin‐inducible gene, was constitutively activated in ebp1 transfectants as determined by reporter construct analysis. These data demonstrate that ectopic expression of the ErbB‐3 binding protein Ebp1 inhibits proliferation and induces differentiation of ErbB‐2, ErbB‐3–expressing human breast carcinoma cell lines. J. Cell. Physiol. 183:321–329, 2000.