δEF1 down-regulates ER-α expression and confers tamoxifen resistance in breast cancer.

ABSTRACT: Resistance to tamoxifen therapy represents a major barrier to the successful treatment of breast cancer, where a loss of or reduced ER-α level is considered a primary mechanism. Understanding how ER-α expression is regulated would provide insights into new intervention points to overcome tamoxifen resistance. In this study, we report that the expression of δEF1 is up-regulated by 17β-estradiol (E2) in MCF-7 cells in an ER-α-dependent manner, through either PI3K or NF-κB pathway. Ectopic expression of δEF1 in turn repressed ER-α transcription by binding to the E(2)-box on the ER-α promoter. At the tissue level of breast cancer, there is a strong and inverse correlation between the expression levels of δEF1 and ER-α. In MCF-7 cells, an elevated expression of δEF1 made the cells less sensitiv

SUBMITTER: Guo S 

PROVIDER: S-EPMC3528679 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature