Abstract 3115: Role of nuclear coactivator AIB1 in endothelial cell function and angiogenesis

Abstract

Abstract The nuclear receptor coactivator oncogene AIB1 (Amplified In Breast Cancer 1) has a clearly defined role in steroid and growth factor signaling in epithelial cells of cancers. Recently, we have demonstrated that AIB1 is functionally required for HER2-mediated mammary tumorigenesis in MMTV/Neu mouse model for breast cancer through regulation of HER2 phosphorylation and signaling. Generation of neu/HER2 transgenic mice with either loss of one or both copies of the AIB1 gene resulted in reduced or complete abolition of mammary tumor development, respectively. One very interesting aspect of this study was that the tumors that arose in HER2 AIB1 HET (+/-) mice were phenotypically different from those in HER2 AIB1 WT (+/+) mice in that they were smaller, more necrotic and significantly less vascularized. This data indicated to us the possibility that the role of AIB1 was not confined to the mammary epithelium proliferation but also had major effects on the surrounding stromal cells. In addition, recent expression array data indicated that AIB1 is also overexpressed in human breast cancer stroma which includes the endothelium. In here, we examined the role of AIB1 in endothelial cell function. We demonstrate that reduction of AIB1 levels in endothelial cells cultured in vitro prevents their ability to form endothelial tubes, in conjuction with reduced proliferation and motility. Furthermore, in ECIS (Electric Cell-substrate Impedance Sensing) assay, HUVEC cells with low AIB1 expression loss the ability to form a monolayer on the surface of gold-film electrodes. Consistent with the reduced proliferation that we observed, cDNA array analysis that compared gene expression patterns of HUVEC cells +/- AIB1 shRNA indicates that a number of key cell cycle regulatory genes and cytokines were regulated by reduction in AIB1 levels. Overall these data describe a new role for nuclear receptor coactivator AIB1 in the endothelium. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3115. doi:10.1158/1538-7445.AM2011-3115