Interrogating Estrogen Receptor α Signaling in Breast Cancer by Chromatin Immunoprecipitation Microarrays

Breast cancer growth is regulated by the coordinated action of estrogen receptor UPalpha and multiple signaling pathways. Profiling of estrogen-regulated gene expression provides mechanisms on estrogenic control of proliferation in breast cancer cells. However, little is known of the hierarchy and the trans-acting factors in ER UPalpha signaling network. Chromatin immunoprecipitation microarray (or ChIP-chip) has emerged as a powerful technique to identify the binding sites of transcription factors and profile the histone modifications in a genome-wide scale. This technology permits, for the first time, comprehensive identification and characterization of direct ERα target genes. Recruitment of ERα to the genome does not only occur at proximal promoter regions, but also involves distal enhancer elements. By using integrated ChIP-chip and bioinformatics analyses, new transcription factor partners (FoxA1 and c-MYC) are being uncovered that play critical roles in ERα -mediated transcription. Based on these findings, a model is constructed to show the complex network of ERα signaling. These new insights will support the development of more precise therapeutic regimen for breast cancer treatment.