MACROD2 overexpression mediates estrogen independent growth and tamoxifen resistance in breast cancers

摘要: Tamoxifen is effective for treating estrogen receptor-alpha (ER) positive breast cancers. However, few molecular mediators of tamoxifen resistance have been elucidated. Here we describe a previously unidentified gene, MACROD2 that confers and independent growth. We found amplified overexpressed in metastatic tamoxifen-resistant tumors. Transgene overexpression cancer cell lines results resistance, whereas RNAi-mediated gene knock down reverses this phenotype. also leads to growth xenograft assays. Mechanistically, increases p300 binding response elements subset ER regulated genes. Primary cancers matched metastases demonstrate expression can change with disease evolution, increased amplification primary tumors associated worse overall survival. These studies establish as key mediator well potential novel target diagnostics therapy.