Metastasis-associated protein 2 is a repressor of estrogen receptor α whose overexpression leads to estrogen-independent growth of human breast cancer cells

Estrogen receptor ( ER)alpha activity is controlled by the balance of coactivators and corepressors contained within cells that are recruited into transcriptional complexes. The metastasis-associated protein ( MTA) family has been demonstrated to be associated with breast tumor cell progression and ER alpha activity. We demonstrate that MTA2 expression is correlated with ER alpha protein expression in invasive breast tumors. We show that the MTA2 family member can bind to ER alpha and repress its activity in human breast cancer cells. Furthermore, it can inhibit ER alpha-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 ER alpha protein, potentially through its associated histone deacetylase complex 1 activity. We hypothesize that MTA2 is a repressor of ER alpha activity and that it could represent a new therapeutic target of ER alpha action in human breast tumors.