Abstract 1159: Differential expression of BP1 and associated gene networks in breast cancer of African American women and Caucasian American women

Abstract

Abstract Introduction: BP1 is a transcription factor of the homeobox gene family activated in 89% of the tumors of African American women (AAW) compared with 57% of the tumors of Caucasian American women (CAW). AAW with breast cancer have larger tumors and an almost 50% higher mortality rate than CAW. BP1 expression is also associated with larger and more aggressive tumors, suggesting BP1 may contribute to the aggressiveness of tumors of AAW. Importantly, BP1 appears to be involved in the epithelial to mesenchymal transition (EMT), based on (i) activation of Twist, a trigger of EMT, (ii) decreased expression of epithelial markers, and (iii) increased expression of mesenchymal markers in cells engineered to overexpress BP1; EMT can lead to metastasis. Here we set out to identify molecular pathways underlying the discrepancy of breast cancer aggressiveness in AAW and CAW with particular attention to BP1 regulated pathways. Results: Cell line analysis. We analyzed five cell lines derived from tumors of AAW and five derived from CAW for EMT markers, including E-CADHERIN (epithelial) and VIMENTIN (mesenchymal). Interestingly, in both types of cell lines, two were epithelial, one was mesenchymal, and two were not classifiable. Two of the AAW derived cell lines and three of the CAW derived cell lines were further studied using microarrays. Preliminary analysis revealed that MYC, CASPASE3, and PPARG are overly represented in the cell lines derived from AAW compared to their CAW derived counterparts; these cell lines also overexpress BP1. Further studies will be performed to determine other pathways that may be differentially expressed in the cell lines from AAW and to determine whether BP1 regulates those pathways. Clinical studies. Tumor tissues from AAW and CAW, matched for age and stage of breast cancer, will be immunostained to determine differential expression of BP1 and EMT markers, and genes identified by microarray analysis as being regulated by BP1. Localization studies of BP1 protein revealed that the nuclear membrane stained most intensely for BP1, with nucleus > cellular membrane > cytoplasm staining. Nuclear and cytoplasmic staining for BP1 tended to be less for CAW than AAW. Conclusions: Our data identify several molecular pathways that may be preferentially activated in breast cancer of AAW. Genes that are overexpressed in tumors of AAW compared with tumors of CAW would make good targets for therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1159. doi:1538-7445.AM2012-1159