PRDX6 promotes lung tumor progression via its GPx and iPLA2 activities |
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| Institution: | 1. College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea;2. Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women?s University, Seoul 140-742, Republic of Korea;3. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 150-716, Republic of Korea;1. Laboratory of Veterinary Pathology, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Japan;2. Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt;3. Comparative Cancer Centre, Gifu University, 1-1 Yanagido, Gifu, Japan;1. Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan;2. Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan;3. Department of Obstetrics and Gynecology, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo 162 8655, Japan;1. Faculty of Chemistry and Mineralogy, Institute of Bioanalytical Chemistry, Leipzig, Germany;2. Center for Biotechnology and Biomedicine, Universität Leipzig, Leipzig, Germany;1. Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA;2. Penn Gene Targeting Core and Laboratory of the Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA |
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| Abstract: | PRDX6 is a bifunctional protein with both glutathione peroxidase (GPx) and calcium-independent phospholipase A2 (iPLA2) activities, which are concomitantly increased with the expression of PRDX6. PRDX6 promoted lung tumor growth in an in vivo allograft model. Herein, we further studied the vital roles in tumor progression of PRDX6 in lung cancer using nude mice bearing PRDX6-overexpressing lung cancer cells. Nude mice xenografted with PRDX6 showed increases in tumor size and weight compared to control mice. Histopathological and Western blotting examination demonstrated that expression of proliferating cell nuclear antigen, vascular endothelial growth factor, metalloproteinases 2 and 9, and cyclin-dependent kinases accompanied by increased iPLA2 and GPx activities were increased in the tumor tissues of PRDX6-overexpressing nude mice. In tumor tissues of PRDX6-overexpressing mice, the activation of mitogen-activated protein kinases and AP-1 DNA binding were also increased. The growth of lung cancer cell lines (A549 and NCI-H460) was enhanced by the increase in iPLA2 and GPx activities of PRDX6. In addition, mutant PRDX6 (C47S) attenuated PRDX6-mediated p38, ERK1/2, and AP-1 activities as well as its enzyme activities in the A549 and NCI-H460 lines. Furthermore, tumor growth and p38, ERK1/2, and AP-1 activities were also inhibited in nude mice bearing mutant PRDX6 (C47S) compared to PRDX6. Therefore, our findings indicate that PRDX6 promotes lung tumor growth via increased glutathione peroxidase and iPLA2 activities. |
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| Keywords: | PRDX6 iPLA2 GPx MAPK AP-1 Free radicals |
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