The goal of this hypothesis development project is 1 to determine if ectopic expression of LINE-1 elements in prostate cancer contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have RNA-sequencing data that we are part way through processing, but suggests so far significant activation of non-coding RNA-sequences derived from RNA from a lymph node metastasis from the prostate. Furthermore, we have subcloned a LINE-1 Open reading frame sequence and will determine the effect of its expression in non-tumorigenic prostate cells. Finally, we have cloned the PIWIL-1 gene, known as a repressor of LINE-1 retroelement sequences in the testis, and have it under the control of a doxycycline-inducible promoter in a lentiviral system, and expressed this inLNCaP and PC-3 prostate cancer cells. Experiments are ongoing to determine if PIWIL-1expression in prostate cancer cells will reduce their growth, thereby providing proof of principle for future gene-based therapeutics for this cancer.