title: PRDX6 promotes lung tumor progression via its GPx and iPLA2 activities.
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.
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors: Hyung-Mun
authors: HM
authors: Yun
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors: Kyung-Ran
authors: KR
authors: Park
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors: Hee Peum
authors: HP
authors: Lee
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors: Dong Hun
authors: DH
authors: Lee
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors: Miran
authors: M
authors: Jo
authors: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women׳s University, Seoul 140-742, Republic of Korea.
authors: Dea Hwan
authors: DH
authors: Shin
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 150-716, Republic of Korea.
authors: Do-Young
authors: DY
authors: Yoon
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea. Electronic address: shan@cbnu.ac.kr.
authors: Sang Bae
authors: SB
authors: Han
authors: College of Pharmacy & Medical Research Center, Chungbuk National University, Chungbuk 361-763, Republic of Korea. Electronic address: jinthong@chungbuk.ac.kr.
authors: Jin Tae
authors: JT
authors: Hong
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D054522:Group VI Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1; D023041:Xenograft Model Antitumor Assays
chemical_list: D018808:Transcription Factor AP-1; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D005979:Glutathione Peroxidase; D020928:Mitogen-Activated Protein Kinases; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: AP-1; Free radicals; GPx; MAPK; PRDX6; iPLA2