Abstract B58: Differential mechanisms control steady state expression of breast cancer antiestrogen resistance 3 (BCAR3) in non-invasive and invasive breast cancer cell lines

Abstract

Abstract The overexpression of breast cancer antiestrogen resistance 3 (BCAR3) has been shown to reduce the antagonistic effects of tamoxifen and fulvestrant in estrogen receptor positive (ER+) breast cancer cell lines. BCAR3 also has a role in the regulation of the migratory and invasive potential of both ER+ and ER- breast cancer cells. A tight correlation between BCAR3 expression and breast cancer cell phenotype exists such that non-invasive, early stage cells express very low levels whereas more invasive, mesenchymal-like cells express very high levels of BCAR3. Because of this correlation, it is important to understand the temporal and spatial regulation of BCAR3. In this study, we set out to define potential mechanisms that regulate BCAR3 expression to better understand, predict, and reverse the consequences of elevated expression. In MCF7 and T47D cells (non-invasive, early stage ER+), high plating density coincident with abundant cell-cell junctions resulted in low levels of both BCAR3 mRNA and protein. Conversely, BCAR3 expression was found to be elevated under conditions in which cell-cell junctions were reduced (low density plating). In the more invasive BT549 and MDA-MB-231 cell lines, BCAR3 mRNA and protein expression was found to be dependent upon the stable expression of its binding partner p130Cas (Cas). Interestingly, we previously showed that BCAR3 expression positively correlates with the tyrosine phosphorylation state of Cas, activation of the tyrosine kinase c-Src, and the physical interaction between Cas and c-Src. We are currently investigating whether cell-cell junction formation and differential expression alters the subcellular localization of BCAR3. Taken together, we propose a role for BCAR3 in driving the transition from localized disease to a more invasive and aggressive breast tumor phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B58.