Expression and regulation of NDRG2 (N‐myc downstream regulated gene 2) during the differentiation of dendritic cells

Choi, Seung‐Chul; Kim, Kwang Dong; Kim, Jong-Tae; Kim, Jae Wha; Yoon, Do‐Young; Choe, Yong-Kyung; Chang, Yong-Suk; Paik, Sang‐Gi; Lim, Jong‐Seok

doi:10.1016/s0014-5793(03)01030-5

Cited by 88 publications

(76 citation statements)

References 48 publications

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“…Included in this group are N-myc downstream regulated gene 2 (Cluster 6), pigment epitheliumderived factor (Cluster 6), transmembrane protein semaphorin 6C (Cluster 4) and slit-1 (Cluster 6) (Wu et al, 1999;Qu et al, 2002;Choi et al, 2003;Deng et al, 2003;Wang et al, 2003). The last two genes are particularly interesting since both have been typically associated with inhibiting nerve cell migration (Wu et al, 1999;Qu et al, 2002), and our findings suggest that these same genes may hinder cancer cell motility.…”

Section: Discussionmentioning

confidence: 83%

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Teramoto

Castellone

Malek³

et al. 2004

Oncogene

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Activated forms of Ras family members are prevalent in many cancers where Ras mutants transduce signals essential for transformation, angiogenesis, invasion and metastasis. As a cancer progression model, we used NIH3T3 cells to explore the mechanism of Ras-induced tumorigenesis. Ras family mutants H-RasV12 and Rit79L strongly induced foci formation, while Rho family mutants RhoA-QL, Rac1-QL and Cdc42-QL were less effective. A comparison of downstream transcriptional targets of Ras and Rho family members using a 26 383 element cDNA microarray revealed that the osteopontin (OPN) gene exhibited the best correlation between magnitude of gene expression change and level of foci formation (r ¼ 0.96, Po0.001). In association with H-RasV12-and Rit79L-mediated transformation, foci secreted OPN protein and upregulated the OPN receptor CD44, suggesting the novel initiation of an aberrant OPN-CD44-Rac autocrine pathway. In support of this were the following observations. First, RGD-deficient OPN protein-binding activity was present in H-RasV12-transformed cells but not in control cells, and binding activity was inhibited by the CD44 blocking antibody. Second, foci formation, cell invasion and Rac activity were induced by H-RasV12 and inhibited by the CD44 blocking antibody. Third, foci formation by H-RasV12 was substantially reduced by a short interfering RNA (siRNA) specifically targeting OPN expression for knockdown. Fourth, H-RasV12-mediated transformation was not blocked by the GRGDS peptide, suggesting that OPN effects were not mediated by the integrins. Lastly, OPN knockdown affected the downstream expression of 160 '2nd tier' genes, and at least a subset of these genes appears to be involved in transformation. Indeed, four genes were selected for knockdown, each resulting in a disruption of foci formation and/or invasion. These results underscore the role of aberrant autocrine signaling and transcriptional networking during tumorigenesis.

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Section: Discussionmentioning

confidence: 83%

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Teramoto

Castellone

Malek³

et al. 2004

Oncogene

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“…NDRG2 expression is upregulated in cortical pyramidal neurons, senile plaques, and the cellular process of dystrophic neurons in the Alzheimer's brain, whereas expression is decreased in the rat frontal cortex after antidepressant treatment and electroconvulsive therapy (11). NDRG2 also plays a role in aldosterone-mediated epithelial sodium channel function (12), dendritic cell differentiation (13), and insulin action (14). NDRG3, on the other hand, may play a role in spermatogenesis because it is found in the outer layers of the seminiferous epithelium (3).…”

Section: N-myc Downstream-regulated Gene (Ndrg)mentioning

confidence: 99%

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Yamamoto

Kokame

Okuda

et al. 2011

Journal of Biological Chemistry

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The N-myc downstream-regulated gene (NDRG) family consists of four related proteins, NDRG1-NDRG4, in mammals. We previously generated NDRG1-deficient mice that were unable to maintain myelin sheaths in peripheral nerves. This condition was consistent with human hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, caused by a nonsense mutation of NDRG1. In contrast, the effects of genetic defects of the other NDRG members remain unknown. In this study, we focused on NDRG4, which is specifically expressed in the brain and heart. In situ mRNA hybridization on the brain revealed that NDRG4 was expressed in neurons of various areas. We generated NDRG4-deficient mice that were born normally with the expected Mendelian frequency. Immunochemical analysis demonstrated that the cortex of the NDRG4-deficient mice contained decreased levels of brain-derived neurotrophic factor (BDNF) and normal levels of glial cell line-derived neurotrophic factor, NGF, neurotrophin-3, and TGF-␤1. Consistent with BDNF reduction, NDRG4-deficient mice had impaired spatial learning and memory but normal motor function in the Morris water maze test. When temporary focal ischemia of the brain was induced, the sizes of the infarct lesions were larger, and the neurological deficits were more severe in NDRG4-deficient mice compared with the control mice. These findings indicate that NDRG4 contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress. N-myc downstream-regulated gene (NDRG)3 family members NDRG1-NDRG4 are intracellular proteins, consist of 340 -394 amino acid residues, and share 53-65% sequence identity with each other. Furthermore, accumulating evidence implicates their roles in development, cancer metastasis, and the immune system (1-5).We originally identified RTP (NDRG1) as a homocysteineresponsive gene in human umbilical vein endothelial cells (6), which is also called DRG1, Cap43, Rit42, Ndr1, and PROXY-1. NDRG1 expression is induced by a number of conditions, such as DNA damage, hypoxia, and intracellular calcium ion elevation (4). Overexpression of NDRG1 suppresses the metastatic potency of some types of cancer cells (4) and enhances the degranulation of mast cells in response to various stimuli (7). A nonsense mutation of NDRG1 causes hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, which presents as distal muscle wasting and atrophy, foot and hand deformities, tendon areflexia, sensory loss, and deafness in afflicted individuals (8). We previously generated NDRG1-deficient mice and revealed the essential role of NDRG1 in the cytoplasm of Schwann cells for the maintenance of myelin sheaths in peripheral nerves (9). A frame shift deletion of Ndrg1 in Greyhounds also causes polyneuropathy (10).Similar to NDRG1, the expression of NDRG2 is induced by stress conditions such as hypoxia (1). NDRG2 expression is upregulated in cort...

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“…Northern blot analysis was performed according to a previously described method (Choi et al, 2003). The NDRG2 probe was prepared from the RT-PCR product using a specific primer set; 5'-ATGGCGGAGCTGCAGG-3' and 3'-TCAACAGGAGACCTCCAT-5'.…”

Section: Northern Blot Analysismentioning

confidence: 99%

“…NDRG2 has been implicated in cell growth (Deng et al, 2003), differentiation (Choi et al, 2003), and apoptosis (Zhou et al, 2001). It has also been reported that NDRG2 is rapidly responsive to mineralocorticoid stimuli in the kidney (Boulkroun et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death

Choi

Yoon²,

Park³

et al. 2007

Exp Mol Med

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Although N-myc downstream regulated gene 2 (NDRG2) has been known to be a tumor suppressor gene, the function of this gene has not been elucidated. In the present study, we investigated the expression and function of NDRG2 in human gastric cancer. Among seven gastric cancer and two non-cancer cell lines, only two gastric cancer cell lines, SNU-16 and SNU-620, expressed NDRG2, which was detected in the cytoplasm. Interestingly, NDRG2 was highly expressed in normal gastric tissues, but gastric cancer patients were divided into NDRG2-positive and -negative groups. The survival rate of NDRG2-negative patients was lower than that of NDRG2-positive patients. We confirmed that the loss of NDRG2 expression was a significant and independent prognostic indicator in gastric carcinomas by multivariate analysis. To investigate the role of NDRG2 in gastric cancer cells, we generated a NDRG2-silenced gastric cancer cell line, which stably expresses NDRG2 siRNA. NDRG2-silenced SNU-620 cells exhibited slightly increased proliferation and cisplatin resistance. In addition, inhibition of NDRG2 decreased Fas expression and Fas-mediated cell death. Taken together, these data suggest that inactivation of NDRG2 may elicit resistance against anticancer drug and Fas-mediated cell death. Furthermore, case studies of gastric cancer patients indicate that NDRG2 expression may be involved in tumor progression and overall survival of the patients.

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Expression and regulation of NDRG2 (N‐myc downstream regulated gene 2) during the differentiation of dendritic cells

Cited by 88 publications

References 48 publications

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death

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