Project description:ETS transcription factors have recently emerged as important elements in the pathogenesis of prostate cancer (PCa). ETS gene rearrangements leading to over-expression of ETS factors, like ERG, ETV1 and ETV4, are found in about 50% of prostate tumors. While the oncogenic potential of translocated ETS has been demonstrated in several contexts, the impact of endogenously expressed ETS factors on prostate tumorigenesis has been largely overlooked. Here we show that the epithelial-specific ETS factor ESE3, which is normally expressed in basal prostate epithelial (PrE) cells and frequently down-regulated in prostate tumors, serves as gatekeeper to maintain cell differentiation and its down-regulation leads to the acquisition of mesenchymal, stem cell (SC) and tumorigenic properties. ESE3 exerts this function by regulating critical genes involved in the epithelial to mesenchymal transition (EMT) and cell “stemness” and maintaining the equilibrium between cell differentiation and proliferation. Loss of ESE3 may be an important step in prostate tumorigenesis. Keywords: prostate epithelial cells, prostate cancer, gene expression profiling, ETS genes, EMT, cancer stem cells
