Androgen receptor (AR) is expressed in more than 80% of ER-positive breast cancer and its expression is correlated with better prognosis in ER-positive breast cancer. However, little is known about the regulation of AR expression in breast cancer. We have previously reported that metastasis-associated protein 1 (MTA1), a cancer-promoting gene that is overexpressed in breast cancer, increases the expression of ERα in breast cancer. Here, we investigated the role of MTA1 on AR expression in three different ER-positive breast cancer cell lines. First, small interfering RNA-mediated knockdown of MTA1 increased protein and mRNA expression of AR in MCF7, T47D, and ZR75-1. Overexpression of MTA1 down-regulated expression of AR in these cell lines. Activity of the reporter-encoding AR promoter (-2408 bp ~ +1126 bp) was decreased in the presence of MTA1 in a dose-dependent manner. Analysis of the chromatin immunoprecipitation sequencing data (http://encodeproject.org/ENCODE) revealed that MTA1 may bind to 1 kilo base downstream of AR transcription start site. Together, our results demonstrated that MTA1 negatively regulates expression of AR in breast cancer cells. These results suggest that the negative regulation of AR may be associated with the cancer promoting effects of MTA1, which may provide a therapeutic opportunity against ER-positive breast cancer.

Citation Format: SeungSu Kim. Metastasis-associated protein 1 negatively regulates expression of androgen receptor in ER-positive breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3607. doi:10.1158/1538-7445.AM2017-3607