Expression of NAG-1, a Transforming Growth Factor-β Superfamily Member, by Troglitazone Requires the Early Growth Response Gene EGR-1

Baek, Seung Joon; Kim, Jongsik; Nixon, Jennifer B.; DiAugustine, Richard P.; Eling, Thomas E.

doi:10.1074/jbc.m305295200

Cited by 135 publications

(122 citation statements)

References 56 publications

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“…In Ding's study, MIC-1 production in human adipocytes was stimulated by H 2 O 2 indicating a possible involvement of oxidative stress in the induction of MIC-1 synthesis. Furthermore, 15d-prostaglandin J(2) has been reported to induce MIC-1 protein expression, promoting apoptosis in cancer cells (17) and the same was true for stimulation of MIC-1 production in human adipocytes in Ding's study. Taken together, these data suggest that oxidative stress might be an important inducer of MIC-1 production.…”

Section: Discussionmentioning

confidence: 54%

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Dostálová

Roubíček²,

Bartlova³

et al. 2009

European Journal of Endocrinology

148

140

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Objective: Macrophage inhibitory cytokine-1 (MIC-1) is a novel regulator of energy homeostasis. We explored whether alterations in MIC-1 levels contribute to metabolic disturbances in patients with obesity and/or obesity and type 2 diabetes mellitus (T2DM). Design: We measured serum MIC-1 levels and its mRNA expression in subcutaneous and visceral adipose tissue of 17 obese nondiabetic women, 14 obese women with T2DM and 23 healthy lean women. We also explored the relationship of MIC-1 with anthropometric and biochemical parameters and studied the influence of 2-week very low calorie diet (VLCD) on serum MIC-1 levels. Methods: Serum MIC-1 levels were measured by ELISA and its mRNA expression was determined by RT-PCR. Results: Both obese and T2DM group had significantly elevated serum MIC-1 levels relative to controls. T2DM group had significantly higher serum MIC-1 levels relative to obese group. Serum MIC-1 positively correlated with body weight, body fat, and serum levels of triglycerides, glucose, HbAlc, and C-reactive protein and it was inversely related to serum high-density lipoprotein cholesterol. Fat mRNA MIC-1 expression did not significantly differ between lean and obese women but it was significantly higher in subcutaneous than in visceral fat in both groups. VLCD significantly increased serum MIC-1 levels in obese but not T2DM group. Conclusion: Elevated MIC-1 levels in patients with obesity are further increased by the presence of T2DM. We suggest that in contrast to patients with cancer cachexia, increased MIC-1 levels in obese patients and diabetic patients do not induce weight loss.

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Section: Discussionmentioning

confidence: 54%

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Dostálová

Roubíček²,

Bartlova³

et al. 2009

European Journal of Endocrinology

148

140

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“…40 Egr-1 has been designated as one of the upstream activators of NAG-1. 8 Our results demonstrate that Egr-1 protein expression and DNA binding activity were increased after 1 hr of AST incubation, which occurred at the time before the activation of NAG-1 expression. It is therefore plausible that AST-induced NAG-1 overexpression could involve prior activation of Egr-1 at the transcriptional level.…”

Section: Discussionmentioning

confidence: 58%

“…6 Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) is a novel therapeutic target which contributes to the antitumorigenic and proapoptotic effects in various cancer cells. [7][8][9][10] As previously reported, the anticancer activities of several compounds obtained from natural sources could be associated with NAG-1 induction. 7,[11][12][13] Initially, NAG-1 was found to be induced in a p53-dependent manner and therefore considered as a biomarker for p53 activation.…”

mentioning

confidence: 70%

“…14,15 Nevertheless, later discovery indicated that basal transcription of NAG-1 can also be regulated by several other regulatory elements in its promoter region, of which its expression requires the transcription factor early growth response gene (Egr-1). 8,16 Current study further suggests that NAG-1 could be a downstream target of the PI3K-Akt signaling pathway. 17 The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling has been known as an important regulator of cell proliferation and survival.…”

mentioning

confidence: 99%

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A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Auyeung

Cho

2009

Intl Journal of Cancer

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Astragalus membranaceus has been used to ameliorate the side effects of antineoplastic drugs because of its immunomodulating nature. We had recently demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and proapoptotic properties in human colon cancer cells and tumor xenograft. In this study, we identified NSAID-activated gene (NAG-1) as a potential molecular target of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V-FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase reporter assay and electrophoretic mobility shift assay were conducted to determine the association of NAG-1 and related transcription factors with AST during its regulation of apoptotic activities. Moreover, the combined proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K-Akt pathway were also examined. AST caused overexpression of NAG-1, leading to PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug was associated with increased gene expression, in addition to prior increase in Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was intensified when PI3K inhibitor LY294002 or Akt inhibitor was cotreated and reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG-1 is a potential molecular target of AST in its antitumorigenic and proapoptotic actions, which would have additive effects when used along with PI3K-Akt inhibitors. The information obtained could facilitate future development of a novel target-specific chemotherapeutic agent with known molecular pathway. ' 2009 UICC

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“…NAG-1 is up-regulated by a number of anti-tumorigenic compounds in addition to NSAIDs, including peroxisome proliferator-activated receptor γ (PPARγ) ligands (Baek et al, 2003;2004b;Yamaguchi et al, 2006a), phosphatidylinositol 3-kinase inhibitor (Yamaguchi et al, 2004) and chemopreventive dietary compounds, such as resveratrol (Baek et al, 2002a), indole-3-carbinol , conjugated linoleic acid (Lee et al, 2006) and epicatechin gallate (Baek et al, 2004a), as well as anti-inflammatory plant extracts (Yamaguchi et al, 2006b). Interestingly, induction of NAG-1 by these compounds occurs by multiple mechanisms at the levels of transcription and post-transcription.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

Yamaguchi

Whitlock

Liggett

et al. 2008

The Veterinary Journal

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Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a divergent member of the transforming growth factor β superfamily, was previously identified as a gene induced by several anti-tumorigenic compounds, including NSAIDs and peroxisome proliferator-activated receptor γ (PPARγ) ligands in humans. In this study, canine NAG-1 was characterised from a canine genomic database. Gene induction by some NSAIDs and PPARγ ligands was demonstrated in canine osteosarcoma cell lines. Phylogenetic analysis indicates that canine NAG-1 is more homologous with the corresponding mouse and rat genes than with human NAG-1. Expression of canine NAG-1 was increased by treatment with piroxicam and SC-560 (NSAIDs) and the PPARγ ligand rosiglitazone. This study demonstrates that canine NAG-1 is up-regulated by some anti-tumorigenic compounds in osteosarcoma cell lines and may provide an important target of chemotherapy in canine cancer.

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Expression of NAG-1, a Transforming Growth Factor-β Superfamily Member, by Troglitazone Requires the Early Growth Response Gene EGR-1

Cited by 135 publications

References 56 publications

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

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