Abstract
Abstract Timing, mode and amplitude of gene regulation depend on the tissue specific dynamic composition of transcription factor complexes. Abnormalities of the constituents of the complex are expected to modify the regulatory behavior of the entire module. Here we report a novel E2F-ETS proliferation control module in Ewing's sarcoma. FLI1 and other ETS factors are frequently found to be fused to EWS in this highly aggressive pediatric cancer of the bone. In a genome-wide localization analysis of EWS/FLI1 as well as E2F3 by ChipSeq, two patterns associated with distinct gene sets and modes of regulation were identified and integrated with gene expression data. EWS/FLI1 significantly colocalized with E2F3 to proximal promoters of activated proliferation genes while EWS/FLI1 binding independent of E2F3 occurred predominantly distant to repressed differentiation genes. We find that this key module of the transcription factor network underlying Ewing's sarcoma is of general importance and not limited to this specific ETS driven neoplasm. Recently, prostate cancer was shown to frequently harbor fusions of the ERG gene. Here we demonstrate that the ETS/E2F3 complex is also present in VCap prostate cancer cells, identify a common set of genes responsive to this module and computationally show that this set of core-responders is involved in proliferation control and translation. Acknowledgement: This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. 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 1285. doi:1538-7445.AM2012-1285
Published Version
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