Abstract 5001: Epigenetic networks in breast cancer

Abstract

Abstract Epigenetic mechanisms are essential for normal development and maintenance of normal gene expression patterns in humans. Recent studies suggest that epigenetic alterations may be the key initiating events in some forms of cancers and global changes in the epigenome are a hallmark of cancers. Phospholipase D (PLD) catalyzes the hydrolysis of phophatidylcholine to generate the lipid second messenger phosphatidic acid (PA) and choline and regulates multiple cellular pathways. Elevated expression of PLD1 promoted cell proliferation and has been associated with the progression and metastasis of multiple cancers. In this work, we showcased the applications of our new epigenetic tools by elucidating the changes in chromatin organization (3C), DNA methylation and microRNA expression that underlies the aberrant expression level of PLD1 in breast cancers. Differences in PLD1 expression and the epigenetic network between tamoxifen responsive (MCF-7) and non-responsive (MDA-MB-231) breast cancer cell lines were compared to associate epigenetic changes with their cancer phenotypes. Effects of DNA demethylation and histone acetylation induced by methyltransferase inhibitor (5-aza-2′-deoxycytidine) and histone deacetylase inhibitor (Trichostatin A) were also investigated to provide insights into the molecular mechanisms of epigenetic drugs. 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 5001. doi:1538-7445.AM2012-5001