Regulation of EP4 expression via the Sp-1 transcription factor: Inhibition of expression by anti-cancer agents

Kambe, Atsushi; Iguchi, Genzo; Moon, Yuseok; Kamitani, Hideki; Watanabe, Takashi; Eling, Thomas E.

doi:10.1016/j.bbamcr.2008.01.032

Cited by 29 publications

(51 citation statements)

References 37 publications

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“…Afterwards, the PBS was aspirated and added Bio-Rad Gene Pulser electroporation buffer. After resuspending the cells, the desired control or IGFBP1 expression vectors (IGFBP1-pCMV6-AC-GFP) purchased from OriGene Technologies, Inc. (Rockville, MD, USA), or control (pcDNA3.1), Sp1 overexpression pcDNA3.1Sp1/flu vector (kindly provided by Dr. Thomas E. Eling, National Institute of Environmental Health Sciences, USA) [29], at a final concentration of 2 µg/mL were added and the electroporation plate were put in the MX cell plate chamber and closed the lid in Gene Pulser II Electroporation System (Bio-Rad, Hercules, CA, USA). The electroporation conditions on the plates to deliver 148 V/5 ms square wave were adjusted until reaching the optimum.…”

Section: Methodsmentioning

confidence: 99%

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Tang¹,

Wu²,

Zheng³

et al. 2017

Cell Physiol Biochem

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Background: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1. QRT-PCR was used to examine the mRNA levels of the IGFBP1 gene. Small interfering RNAs (siRNAs) were used to knockdown PPARγ and IGFBP1 genes. Exogenously expression of IGFBP1 and Sp1 was determined by transient transfection assays. IGFBP1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. In vivo nude mice xenograft model and bioluminescent imaging system were used to confirm the findings. Results: We showed that emodin induced cell cycle arrest of NSCLC cells. Emodin increased PPARγ protein and luciferase reporter activity, which were abolished by inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK and AMPK. Silencing of PPARγ abrogated emodin-inhibited cell growth and cell cycle arrest. Furthermore, emodin elevated IGFBP1 mRNA, protein, and promoter activity through activation of PPARγ. Intriguingly, overexpressed Sp1 attenuated emodin-induced IGFBP1 expression, which was not observed in cells with silenced PPARγ gene. Moreover, silencing of IGFBP1 gene blunted emodin-induced inhibition of cell growth and cell cycle arrest. On the contrary, overexpressed IGFBP1 enhanced emodin-induced phosphorylation of AMPKα and ERK1/2, and restored emodin-inhibited growth in cells with silenced endogenous IGFBP1 gene. Emodin also inhibited growth of lung xenograft tumors and Sp1, and increased IGFBP1 and PPARγ protein expressions In vivo. Conclusion: Collectively, our results show that emodin inhibits growth of non-small-cell lung cancer (NSCLC) cells through ERK and AMPKα-mediated induction of PPARγ, followed by reduction of Sp1. This in turn induces IGFBP1 gene expression. Thus, the signaling cascades, positive feedback loop and cooperative interplay between transcription factors-induced the expression of IGFBP1 gene contribute to the overall responses of emodin. This study provides a novel mechanism by which emodin inhibits growth of human lung cancer cells.

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Section: Methodsmentioning

confidence: 99%

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Tang¹,

Wu²,

Zheng³

et al. 2017

Cell Physiol Biochem

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“…H 2 O 2 caused phosphorylation of ERK1/2 and MEK1, thus altered the phosphorylation state of Sp1. Moreover, ERK was found to decrease binding of Sp1 to the prostaglandin E receptor 4 (EP4) promoter by phosphorylating Spproteins, thereby leading to suppression of EP4 in human glioblastoma cells (Kambe et al, 2008). The Thr 453 and Thr 739 residues of Sp1 were identified as the phosphorylation sites in response to ERK activation (Milanini-Mongiat et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

Regulation of RASSF1A in nasopharyngeal cells and its response to UV irradiation

Lee

Chow

et al. 2009

Gene

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“…05 compared with the control group. glioblastoma cells (Kambe et al 2008). Therefore, we hypothesized that adiponectin regulates the gene transcription of KISS1 and the onset of puberty through AMPK and the activity of its downstream signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons

Wen

Liu²,

Bi³

et al. 2012

Journal of Endocrinology

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Adiponectin secreted from adipose tissues plays a role in the regulation of energy homeostasis, food intake, and reproduction in the hypothalamus. We have previously demonstrated that adiponectin significantly inhibited GNRH secretion from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an artificial AMPK activator, decreased KISS1 mRNA transcription and promoter activity. Conversely, inhibition of AMPK by Compound C or AMPKa1-SiRNA augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm to nucleus; however, Compound C and AMPKa1-siRNA played an inverse role. Our experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated twofold in the Compound C-treated rats and decreased about 60-70% in gAd-or AICAR-treated rats compared with control group. The numbers of kisspeptin immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different treatments. In conclusion, our results provide the first evidence that adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of AMPK and subsequently decreased translocation of SP1.

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Regulation of EP4 expression via the Sp-1 transcription factor: Inhibition of expression by anti-cancer agents

Cited by 29 publications

References 37 publications

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Regulation of RASSF1A in nasopharyngeal cells and its response to UV irradiation

Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons

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