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

Chiou SS, Wang SS, Wu DC, Lin YC, Kao LP, Kuo KK, Wu CC, Chai CY, Lin CL, Lee CY, Liao YM, Wuputra K, Yang YH, Wang SW, Ku CC, Nakamura Y, Saito S, Hasegawa H, Yamaguchi N, Miyoshi H, Lin CS, Eckner R, Yokoyama KK - Cancers (Basel) (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chiouss@kmu.edu.tw.

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.

No MeSH data available.


Related in: MedlinePlus

Tumor formation of DAOY, 2F- or 4F-iPSC-like cells in SCID mice. (A) Time course of tumor sizes in the SCID mice with subcutaneously injected with DAOY, 2F-iPSC-like cells (2F), and 4F-iPSC-like cells (4F). Tumor sizes were measured as indicated in Experimental Sections. The tumor sizes were getting bigger on 28 days after transplantation. (B) Tumors of DAOY (left), 2F-iPSC-like cells, 4F-iPSC-like cells were shown (right). Scale bars showed the sizes of tumors. (C) Tumors were appeared after day 44 after transplantation (×400 fold). 2F-iPSC-like cells generated malignant tumors with more vessels and giant cells (see arrow), and 4F-iPSC-like cells exhibited more malignant tumors with rapid mitosis and necrosis (see arrows). The black arrows indicted the possible malignant sites.
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cancers-05-00959-f007: Tumor formation of DAOY, 2F- or 4F-iPSC-like cells in SCID mice. (A) Time course of tumor sizes in the SCID mice with subcutaneously injected with DAOY, 2F-iPSC-like cells (2F), and 4F-iPSC-like cells (4F). Tumor sizes were measured as indicated in Experimental Sections. The tumor sizes were getting bigger on 28 days after transplantation. (B) Tumors of DAOY (left), 2F-iPSC-like cells, 4F-iPSC-like cells were shown (right). Scale bars showed the sizes of tumors. (C) Tumors were appeared after day 44 after transplantation (×400 fold). 2F-iPSC-like cells generated malignant tumors with more vessels and giant cells (see arrow), and 4F-iPSC-like cells exhibited more malignant tumors with rapid mitosis and necrosis (see arrows). The black arrows indicted the possible malignant sites.

Mentions: We injected the human iPSC-like cells into SCID mice. Tumor formation was repressed during the initial stage up to 28–35 days after injection; however, beginning 1 month after injection, significant growth occurred, and the tumor size increased by 2.5–3.5-fold (Figure 7A,B). We detected no signs of differentiation but found malignant growth of vessels, giant cell formation, and mitosis in sometimes in 2F- or 4F-iPSC-like cells (Figure 7C). Thus, we found that the teratoma sometimes generated the malignant tumors.


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

Chiou SS, Wang SS, Wu DC, Lin YC, Kao LP, Kuo KK, Wu CC, Chai CY, Lin CL, Lee CY, Liao YM, Wuputra K, Yang YH, Wang SW, Ku CC, Nakamura Y, Saito S, Hasegawa H, Yamaguchi N, Miyoshi H, Lin CS, Eckner R, Yokoyama KK - Cancers (Basel) (2013)

Tumor formation of DAOY, 2F- or 4F-iPSC-like cells in SCID mice. (A) Time course of tumor sizes in the SCID mice with subcutaneously injected with DAOY, 2F-iPSC-like cells (2F), and 4F-iPSC-like cells (4F). Tumor sizes were measured as indicated in Experimental Sections. The tumor sizes were getting bigger on 28 days after transplantation. (B) Tumors of DAOY (left), 2F-iPSC-like cells, 4F-iPSC-like cells were shown (right). Scale bars showed the sizes of tumors. (C) Tumors were appeared after day 44 after transplantation (×400 fold). 2F-iPSC-like cells generated malignant tumors with more vessels and giant cells (see arrow), and 4F-iPSC-like cells exhibited more malignant tumors with rapid mitosis and necrosis (see arrows). The black arrows indicted the possible malignant sites.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795374&req=5

cancers-05-00959-f007: Tumor formation of DAOY, 2F- or 4F-iPSC-like cells in SCID mice. (A) Time course of tumor sizes in the SCID mice with subcutaneously injected with DAOY, 2F-iPSC-like cells (2F), and 4F-iPSC-like cells (4F). Tumor sizes were measured as indicated in Experimental Sections. The tumor sizes were getting bigger on 28 days after transplantation. (B) Tumors of DAOY (left), 2F-iPSC-like cells, 4F-iPSC-like cells were shown (right). Scale bars showed the sizes of tumors. (C) Tumors were appeared after day 44 after transplantation (×400 fold). 2F-iPSC-like cells generated malignant tumors with more vessels and giant cells (see arrow), and 4F-iPSC-like cells exhibited more malignant tumors with rapid mitosis and necrosis (see arrows). The black arrows indicted the possible malignant sites.
Mentions: We injected the human iPSC-like cells into SCID mice. Tumor formation was repressed during the initial stage up to 28–35 days after injection; however, beginning 1 month after injection, significant growth occurred, and the tumor size increased by 2.5–3.5-fold (Figure 7A,B). We detected no signs of differentiation but found malignant growth of vessels, giant cell formation, and mitosis in sometimes in 2F- or 4F-iPSC-like cells (Figure 7C). Thus, we found that the teratoma sometimes generated the malignant tumors.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chiouss@kmu.edu.tw.

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.

No MeSH data available.


Related in: MedlinePlus