The MUC1 protein is aberrantly overexpressed by most human breast carcinomas. We report that the MUC1 C-terminal subunit associates with estrogen receptor α (ERα) and that this interaction is stimulated by 17β-estradiol (E2). MUC1 binds directly to the ERα DNA binding domain and stabilizes ERα by blocking its ubiquitination and degradation. Chromatin immunoprecipitation assays further demonstrate that MUC1 (1) associates with ERα complexes on estrogen-responsive promoters, (2) enhances ERα promoter occupancy, and (3) increases recruitment of the p160 coactivators SRC-1 and GRIP1. In concert with these results, we show that MUC1 stimulates ERα-mediated transcription and contributes to E2-mediated growth and survival of breast cancer cells. These findings provide evidence that MUC1 stabilizes ERα and that this oncoprotein is of importance to the activation of ERα function.
