Small leucine zipper protein functions as a negative regulator of estrogen receptor a in breast cancer

Abstract

The nuclear transcription factor estrogen receptor alpha (ER alpha) plays a critical role in breast cancer progression. ER alpha acts as an important growth stimulatory protein in breast cancer and the expression level of ER alpha is tightly related to the prognosis and treatment of patients. Small leucine zipper protein (sLZIP) functions as a transcriptional cofactor by binding to various nuclear receptors, including glucocorticoid receptor, androgen receptor, and peroxisome proliferator-activated receptor gamma. However, the role of sLZIP in the regulation of ER alpha and its involvement in breast cancer progression is unknown. We found that sLZIP binds to ER alpha and represses the transcriptional activity of ERa in ER alpha-positive breast cancer cells. sLZIP also suppressed the expression of ER alpha target genes. sLZIP disrupted the binding of ER alpha to the estrogen response element of the target gene promoter, resulting in suppression of cell proliferation. sLZIP is a novel co-repressor of ER alpha, and plays a negative role in ER alpha-mediated cell proliferation in breast cancer.