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

Abstract

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.

Correlation between MTA2 overexpression and tumour progression in esophageal squamous cell carcinoma

“…Through gene expression profiling studies, metastasis-associated gene 2 (MTA2), a gene involved in the transcriptional silencing machinery of mammalian cells, was recently identified to be significantly overexpressed in metastatic prostate cancer when compared to clinically localized disease (2). MTA2 was identified by differential cDNA library screening of metastatic breast cancer cell lines and confirmed in breast cancer tissue (3). MTA2 overexpression at the transcription level was observed in other cancers, such as gastrointestinal cancers, and was associated with tumour invasiveness and metastasis (4)(5)(6).…”

The human Mi-2/NuRD complex and gene regulation

“…The MTA family is intimately connected to the biology of the estrogen receptor (ER) (Kumar, 2003;Cui et al, 2006) in breast cancer and to mammary gland biology (Manavathi and Kumar, 2007). Two MTA proteins interact directly with the ER itself.…”

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis

“…In addition, MTA1 serves as a transcriptional corepressor of estrogen receptor α (ERα) [31]. MTA2 is also a corepressor of ERα and its overexpression leads to estrogen-independent growth of breast cancer cells [32]. MTA3 is an estrogen-inducible gene [20,33].…”