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

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 ER[alpha] 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.