Free radical biology & medicine, 2015-03, Vol.80, p.136-144
2015
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- Autor(en) / Beteiligte
- Titel
- PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model
- Ist Teil von
- Free radical biology & medicine, 2015-03, Vol.80, p.136-144
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Quelle
- ScienceDirect
- Beschreibungen/Notizen
- Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase (GPx) and iPLA2 activities. Even though several pathophysiological functions have been studied, the definitive role of PRDX6 in tumor growth is not clear. Here, we compared carcinogen-induced tumor growth in PRDX6-transgenic (Tg) mice and non-Tg mice to evaluate the roles of PRDX6 in lung tumor development. Urethane (1g/kg)-induced tumor incidence in PRDX6-Tg mice was significantly higher compared to non-Tg mice. In the tumors of PRDX6-Tg mice, the activation of JAK2/STAT3 and STAT3 DNA binding were also increased, accompanied by increased GPx and iPLA2 activities. PRDX6 was colocalized with JAK2 in tumor tissues and lung cancer cells and also showed physical interaction with JAK2. We found that increasing levels of PRDX6 increase the activation of the JAK2/STAT3 pathway. Furthermore, PRDX6-Tg mice showed altered cytokine levels in the tumors, especially leading to increased CCL5 levels. We validated that the activation of JAK2 was also decreased in lung tumors of CCR5−/− mice, and CCL5 increased the JAK2/STAT3 pathway in the lung cancer cells. Thus, our findings suggest that PRDX6 promotes lung tumor development via its mediated and CCL5-associated activation of the JAK2/STAT3 pathway. [Display omitted] •Increased PRDX6 increases carcinogen-induced tumor growth.•The JAK2/STAT3 pathway is activated in the lung tumor tissue of PRDX6-Tg mice.•iPLA2 and GPx activities are required for the JAK2/STAT3 pathway.•CCL5 is involved in the lung tumor tissues of PRDX6-Tg mice.•Our results provide a novel mechanism for a promoting effect of PRDX6.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0891-5849eISSN: 1873-4596DOI: 10.1016/j.freeradbiomed.2014.12.022Titel-ID: cdi_proquest_miscellaneous_1662003493
- Format
- –
- Schlagworte
- Adenocarcinoma - chemically induced, Adenocarcinoma - enzymology, Adenocarcinoma - genetics, Adenocarcinoma - pathology, Animals, Chemokine CCL5 - genetics, Chemokine CCL5 - metabolism, DNA, Neoplasm - genetics, DNA, Neoplasm - metabolism, Free radicals, Gene Expression Regulation, Neoplastic, Glutathione Peroxidase - genetics, Glutathione Peroxidase - metabolism, GPx, Group VI Phospholipases A2 - genetics, Group VI Phospholipases A2 - metabolism, Injections, Intraperitoneal, iPLA2, JAK2, Janus Kinase 2 - genetics, Janus Kinase 2 - metabolism, Lung cancer, Lung Neoplasms - chemically induced, Lung Neoplasms - enzymology, Lung Neoplasms - genetics, Lung Neoplasms - pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Peroxiredoxin VI - genetics, Peroxiredoxin VI - metabolism, PRDX6, Protein Binding, Receptors, CCR5 - genetics, Receptors, CCR5 - metabolism, Signal Transduction, STAT3, STAT3 Transcription Factor - genetics, STAT3 Transcription Factor - metabolism, Urethane