MUC1 oncoprotein stabilizes and activates estrogen receptor α

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