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Cancers 2013, 5(3), 959-984; doi:10.3390/cancers5030959

Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

1
Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
2
Department of Pediatrics, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan
3
Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
4
School of Dentistry, College of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan
6
Department of Surgery, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
7
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
8
RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan
9
Saito Laboratory of Cell Technology, Yaita, Tochigi 329-1571, Japan
10
Graduate School of Pharmaceutical Science, Chiba University, Chiba 260-8675, Japan
11
Department of Biochemistry & Molecular Biology, UMDNJ-New Jersey Medical School, Newark, NJ 07101, USA
*
Authors to whom correspondence should be addressed.
Received: 3 June 2013 / Revised: 12 July 2013 / Accepted: 18 July 2013 / Published: 26 July 2013
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
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Abstract

We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.
Keywords: anti oxidation; iPSC-like cells; Jun dimerization protein 2; medulloblastoma; ROS; oxidative stress anti oxidation; iPSC-like cells; Jun dimerization protein 2; medulloblastoma; ROS; oxidative stress
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Chiou, S.-S.; Wang, S.S.-W.; Wu, D.-C.; Lin, Y.-C.; Kao, L.-P.; Kuo, K.-K.; Wu, C.-C.; Chai, C.-Y.; Lin, C.-L.S.; Lee, C.-Y.; Liao, Y.-M.; Wuputra, K.; Yang, Y.-H.; Wang, S.-W.; Ku, C.-C.; Nakamura, Y.; Saito, S.; Hasegawa, H.; Yamaguchi, N.; Miyoshi, H.; Lin, C.-S.; Eckner, R.; Yokoyama, K.K. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2. Cancers 2013, 5, 959-984.

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