Metastasis-associated protein 2 is a repressor of estrogen receptor alpha 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 ERalpha activity. We demonstrate that MTA2 expression is correlated with ERalpha protein expression in invasive breast tumors. We show that the MTA2 family member can bind to ERalpha and repress its activity in human breast cancer cells. Furthermore, it can inhibit ERalpha-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 ERalpha protein, potentially through its associated histone deacetylase complex 1 activity. We hypothesize that MTA2 is a repressor of ERalpha activity and that it could represent a new therapeutic target of ERalpha action in human breast tumors.