High expression of peroxiredoxins in prostate cancer cells Free

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The peroxiredoxins (PRDXs), an anti-oxidant protein family composed of six isoforms, called PRDX1-PRDX6, are thought to offer protection to tumor cells in an environment of increased oxidative stress. PRDX6, also known as antioxidant protein 2, is transcriptionally activated by the stress regulated transcription co-activator lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 is upregulated in prostate cancer (PCa) and is likely to promote prostate tumor survival by transcriptionally activating stress and anti-oxidant genes. We hypothesized that because PRDX6 is upregulated by LEDGF/p75, the PRDXs might also be upregulated in PCa cells and promote protection against oxidative stress-induced cell damage. We analyzed by immunoblotting the protein levels of LEDGF/p75 and PRDXs in a panel of prostate cell lines in order to establish a correlation in the expression levels of these proteins. Cell lines included tumor, transformed tumor, transformed non-tumor, benign prostatic hyperplasia and primary prostate. Total protein from cell lines was separated by 4-12% SDS-PAGE, followed by transfer onto PVDF membranes. Protein expressions were detected using specific antibodies to the individual proteins. Similarly, we also analyzed the expression of PRDXs in PC3 prostate tumor cells with small inhibitory RNA (siRNA) mediated LEDGF/p75 knockdown. Additionally expression levels of LEDGF/p75 and PRDX6 was quantified in commercially available PCa tissue micro-arrays. We observed that the PRDXs are expressed at very high levels in the prostate tumor cell lines, as compared to normal or non-tumor transformed cells. Preliminary immunohistochemical analysis of PRDX6 in human prostate tumor tissue arrays revealed high expression of this protein in prostate tumor tissues compared to adjacent normal prostate tissue. However, there was little correlation between the expression levels of LEDGF/p75 and PRDXs in the different prostate cell lines. This was confirmed by the observation that knockdown of LEDGF/p75 in PC3 cells, using siRNA oligos, did not decrease the expression levels of PRDXs. We conclude that while LEDGF/p75 might contribute to the regulation of PRDXs, it may not be essential for controlling their expression in prostate cells. The high PRDX expression in prostate cancer cells may provide a protective mechanism against the augmented state of cellular oxidative stress (ASCOS) in prostate tumors. PRDXs could be attractive targets for novel therapeutic strategies in the treatment of advanced PCa.