title: Lung tumor growth-promoting function of peroxiredoxin 6.
abstract: This study compared lung tumor growth in PRDX6-overexpressing transgenic (Tg) mice and normal mice. These mice expressed elevated levels of PRDX6 mRNA and protein in multiple tissues. In vivo, Tg mice displayed a greater increase in the growth of lung tumor compared with normal mice. Glutathione peroxidase and calcium-independent phospholipase 2 (iPLA2) activities in tumor tissues of Tg mice were much higher than in tumor tissues of normal mice. Higher tumor growth in PRDX6-overexpressing Tg mice was associated with an increase in activating protein-1 (AP-1) DNA-binding activity. Moreover, expression of proliferating cell nuclear antigen, Ki67, vascular endothelial growth factor, c-Jun, c-Fos, metalloproteinase-9, cyclin-dependent kinases, and cyclins was much higher in the tumor tissues of PRDX6-overexpressing Tg mice than in tumor tissues of normal mice. However, the expression of apoptotic regulatory proteins including caspase-3 and Bax was slightly less in the tumor tissues of normal mice. In tumor tissues of PRDX6-overexpressing Tg mice, activation of mitogen-activated protein kinases (MAPKs) was much higher than in normal mice. In cultured lung cancer cells, PRDX6 siRNA suppressed glutathione peroxidase and iPLA2 activities and cancer cell growth, but the enforced overexpression of PRDX6 increased cancer cell growth associated with their increased activities. In vitro, among the tested MAPK inhibitors, c-Jun NH2-terminal kinase (JNK) inhibitor clearly suppressed the growth of lung cancer cells and AP-1 DNA binding, glutathione peroxidase activity, and iPLA2 activity in normal and PRDX6-overexpressing lung cancer cells. These data indicate that overexpression of PRDX6 promotes lung tumor growth via increased glutathione peroxidase and iPLA2 activities through the upregulation of the AP-1 and JNK pathways.
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Miran
authors: M
authors: Jo
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Hyung-Mun
authors: HM
authors: Yun
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Kyung-Ran
authors: KR
authors: Park
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Mi
authors: M
authors: Hee Park
authors: College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.
authors: Tae
authors: T
authors: Myoung Kim
authors: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors: Jhang
authors: J
authors: Ho Pak
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Soo
authors: S
authors: Jae Lee
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Dong Cheul
authors: DC
authors: Moon
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Chun-Woong
authors: CW
authors: Park
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Sukgil
authors: S
authors: Song
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Chong-Kil
authors: CK
authors: Lee
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea.
authors: Sang
authors: S
authors: Bae Han
authors: College of Pharmacy, Medical Research Center, Cheongju, Chungbuk 361-763, Korea. Electronic address: jinthong@chungbuk.ac.kr.
authors: Jin
authors: J
authors: Tae Hong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000032:analysis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054465:Peroxiredoxin VI / Q000032:analysis / Q000502:physiology*; D054467:Phospholipases A2 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018808:Transcription Factor AP-1; D004247:DNA; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D005979:Glutathione Peroxidase; D048031:JNK Mitogen-Activated Protein Kinases; D054467:Phospholipases A2
keywords: AP-1; Free radicals; MAPK; Peroxiredoxin 6