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: Hyung-Mun Yun, Kyung-Ran Park, Hee Peum Lee, Dong Hun Lee, Miran Jo, Dea Hwan Shin, Do-Young Yoon, Sang Bae Han, Jin Tae Hong
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 69 Pg. 367-76 (Apr 2014) ISSN: 1873-4596 [Electronic] United States
• PMID: 24512906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Transcription Factor AP-1
• PRDX6 protein, human
• Peroxiredoxin VI
• Glutathione Peroxidase
• Mitogen-Activated Protein Kinases
• Group VI Phospholipases A2
• PLA2G6 protein, human

Topics

• Animals
• Carcinogenesis
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Glutathione Peroxidase (genetics, metabolism)
• Group VI Phospholipases A2 (genetics, metabolism)
• Humans
• Lung Neoplasms (genetics, pathology)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Peroxiredoxin VI (genetics, metabolism)
• Transcription Factor AP-1
• Xenograft Model Antitumor Assays