Abstract 2924: Metastasis-associated protein 1 induces tamoxifen resistance in MCF7 breast cancer cells

Abstract

Abstract Tamoxifen is most commonly used to treat estrogen receptor-alpha positive breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Metastasis associated protein 1 (MTA1) is a cancer progression-related gene and has been reported to be overexpressed in a variety of human cancers including breast cancer. Here, we showed that transient overexpression of MTA1 in MCF7 breast cancer cells results in tamoxifen resistance, whereas si-RNA mediated knockdown of MTA1 was more susceptible to tamoxifen-induced growth inhibition. Moreover, stable overexpression of MTA1 in MCF7 cells promoted cell proliferation and reduced tamoxifen sensitivity. To explore the mechanisms of MTA1-mediate tamoxifen resistance, we used microarray analysis to profile the gene expression patterns of MTA1 overexpress MCF7 stable cells after tamoxifen treatment. From microarray data analysis, 538 genes were selected as associated with MTA1-mediated tamoxifen resistance (P < 0.05, LPE test; cutoff ≥ 1.5-fold). The Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis revealed that the predominant biological processes associated with these genes are M phase, negative regulation of cell proliferation, mitosis and M phase of mitotic cell cycle. Further, we found that cell-cycle regulator Cyclin D1 and cyclin B1 protein levels were increased in MTA1 overexpression MCF7 stable cells. Analyses of publicly available patient data sets indicated that MTA1 levels are higher in patients after endocrine therapy failure (recurrence), compared to those of responders (non-recurrence). These results suggest that MTA1 may contributed tamoxifen resistance through the regulation of cell cycle components. Citation Format: Min-Ho Lee, Dahae Koh, Mi-Ock Lee. Metastasis-associated protein 1 induces tamoxifen resistance in MCF7 breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2924.