Abstract 4965: The epithelial-specific ETS transcription factor ESE1 links inflammation with prostate cancer transformation and progression

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Altered expression of ETS transcription factors by chromosomal translocation is a frequent event in prostate cancers. However, deregulated expression of other oncogenic ETS factors can be important for the pathogenesis of this disease. By analyzing the expression of multiple ETS genes in prostate cancer and normal prostate by genomic profiling and quantitative real-time PCR we found that the epithelial-specific ETS factor ESE1 was highly expressed (>4 fold) in 44% of prostate tumors compared to normal prostate. ESE1 has been previously shown to be induced by pro-inflammatory stimuli and to regulate the expression of genes involved in inflammation. Treatment of immortalized prostate epithelial cells (LHS) and prostate cancer cells 22RV1 with the pro-inflammatory cytokine IL-1beta induced ESE1 at RNA and protein levels. Concomitantly we observed that cells acquired ability to grow in poly-hema coated plates and an EMT phenotype. To define the role of ESE1 in prostate cancer progression we established 22RV1 prostate cancer cells stably expressing ESE1 (22RV1-ESE1). ESE1 expressing cells were capable to grow in poly-hema coated plates and when injected in nude mice formed larger subcutaneous tumors compared to control cells. Global gene expression profiles indicate robust changes with many genes differentially expressed in 22RV1-ESE1 cells compared to control cells, including key genes involved in cell invasion and metastasis such as COX2 and MMP-10. Consistently, 22RV1-ESE1 cells had greater ability to migrate compared to parental cells in Boyden Chamber and wound-healing assays. Furthermore, when implanted in mice via tail vein injection, 22RV1-ESE1 cells displayed greater ability to form lung metastasis compared to control cells. These results suggest that ESE1 contribute to the acquisition of transforming properties such as the ability to invade and metastasize. Induction of ESE1 during chronic inflammation could be an essential step for prostate cancer initiation and may co-operate with other ETS alterations for prostate cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4965.