Metastasis-Associated Protein 2 is a Repressor of Estrogen Receptor α Whose Overexpression Leads to Estrogen-Independent Growth of Human Breast Cancer Cells

摘要

Estrogen Receptor (ER) α activity is controlled by the balance of coactivators and corepressors contained within cells which are recruited into transcriptional complexes. The metastasis associated (MTA) family of proteins have been demonstrated to be associated with breast tumor cell progression and ERα activity. We show that the MTA2 family member can bind to ERα and repress its activity in human breast cancer cells. Furthermore, it can inhibit ERα mediated colony formation and render breast cancer cells resistant to estradiol and the growth-inhibitory effects of the antiestrogen tamoxifen. MTA2 participates in the deacetylation of ERα protein, potentially through its associated HDAC1 activity. We hypothesize that MTA2 is a repressor of ERα activity and that it could represent a new therapeutic target of ERα action in human breast tumors.