C18

Selective estrogen receptor modulators (SERMs) are used clinically to treat breast cancer as they inhibit estrogen both in promoting cell proliferation and expressing ER-mediated gene expression. However, the complexity of estrogen receptor(ER) biology hinders an effective drug design. Our lab is interested in examining the global ER binding sites and the corresponding gene expression profiles upon treatment of ER by different SERMs.
 Chromatin Immunoprecipitation assays (ChIP) were performed on MCF-7 breast tumor cells in the presence or absence of E2/SERMs or a combination of E2+SERMs. Subsequently, the ChIP samples were applied to Nimblegen tiling arrays, specially customized for ER binding sites, to investigate the different binding profiles. The sources of the probed regions came from ChIP-Clone experiments, ERE motif-finding program and published literature data. This allows for comprehensive survey more than 40,000 highly-putative ER binding sites at once. The array was covered with about 385,000 isothermal probes and each binding region was tiled with at least 6 probes. Nimblegen data obtained with presence or absence of E2 showed high correlations between replicates as well as high consistencies in detection of reported true ER binding sites.
 Affymetrix experiments have been performed with different E2/SERMs treatments across varying time points in MCF-7 cells. The comprehensive expression data will be correlated with the binding profiles to infer direct target genes and functional binding sites.
 Together, the information from binding sites and gene expression profiles upon drug treatments will help to decipher the mechanism of Estrogen Receptor gene regulation over time and over several pharmacologic interventions: E2 and SERMS.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore