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Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

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Technical Report,30 Sep 2014,29 Sep 2015

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University Of Texas Health Science San Antonio United States

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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.

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