COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

doi:10.1186/1471-2407-11-238

Cited by 48 publications

(25 citation statements)

References 29 publications

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“…The inhibition of COX-2 may suppress the growth of HCA-7 and Moser-S colon cancer cells (35). Increased COX-2 activity has a positive effect on the progression of colorectal cancer (36). The present study demonstrated that the expression levels of RhoA and the downstream factors, c-myc, c-fos, and COX-2 proteins, were decreased significantly in vivo due to ART1 gene silencing, and increased with ART1 overexpression in CT26 cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of ART1 on the proliferation and migration of mouse colon carcinoma CT26 cells in vivo

Jian-xia

Xiong

Zeng

et al. 2017

Molecular Medicine Reports

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Arginine-specific mono-ADP-ribosyltransferase 1 (ART1) is an important enzyme that catalyzes arginine-specific mono-ADP-ribosylation. There is evidence that arginine-specific mono-ADP-ribosylation may affect the proliferation of smooth muscle cells via the Rho-dependent signaling pathway. Previous studies have demonstrated that ART1 may have a role in the proliferation, invasion and apoptosis of colon carcinoma in vitro. However, the effect of ART1 on the proliferation and invasion of colon carcinoma in vivo has yet to be elucidated. In the present study, mouse colon carcinoma CT26 cells were infected with a lentivirus to produce ART1 gene silencing or overexpression, and were then subcutaneously transplanted. To observe the effect of ART1 on tumor growth or liver metastasis in vivo, a spleen transplant tumor model of CT26 cells in BALB/c mice was successfully constructed. Expression levels of focal adhesion kinase (FAK), Ras homolog gene family member A (RhoA) and the downstream factors, c-myc, c-fos and cyclooxygenase-2 (COX-2) proteins, were measured in vivo. The results demonstrated that ART1 gene silencing inhibited the growth of the spleen transplanted tumor and its ability to spread to the liver via metastasis. There was also an accompanying increase in expression of FAK, RhoA, c-myc, c-fos and COX-2, whereas CT26 cells with ART1 overexpression demonstrated the opposite effect. These results suggest a potential role for ART1 in the proliferation and invasion of CT26 cells and a possible mechanism in vivo.

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Section: Discussionmentioning

confidence: 99%

Effect of ART1 on the proliferation and migration of mouse colon carcinoma CT26 cells in vivo

Jian-xia

Xiong

Zeng

et al. 2017

Molecular Medicine Reports

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“…Asting et al . observed higher expression of prostaglandin synthetase in CRC cells [ 30 ]. The difference is the result of different populations being studied.…”

Section: Discussionmentioning

confidence: 99%

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp

Szylberg¹,

Janiczek²,

Popiel³

et al. 2016

aoms

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IntroductionColon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps.Material and methodsIn the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16).ResultsStatistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed.ConclusionsExpression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.

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“…Genetic knock-out or pharmacological inhibition of COX-2 has been shown to protect against experimentally-induced carcinogenesis [ 47 ]. Furthermore, more and more studies focus on the announcement of new transcriptional regulators of COX-2 [ 24 , 25 ]. Therefore, it is interesting and more significant to find out the unknown specific factors in regulating COX-2 expression in cancer cells and further explore how COX-2 is activated by these regulatory factors during tumorigenesis and development.…”

Section: Discussionmentioning

confidence: 99%

“…There are CAAT/enhancer binding protein (C/EBP) and cAMP response elements in the 5′-terminal nucleotide sequence. There are also some other protein binding sites in these gene sequences, such as the activator protein-2 (AP-2), the nuclear factor-kappa B (NF-κB) [ 24 , 25 ] and some transcriptional co-activators such as p300/CBP [ 26 , 27 ]. The expression of COX-2 is strictly and specifically regulated by these proteins.…”

Section: Introductionmentioning

confidence: 99%

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth

Xiao

Wang

et al. 2015

Oncotarget

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Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.

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COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

Cited by 48 publications

References 29 publications

Effect of ART1 on the proliferation and migration of mouse colon carcinoma CT26 cells in vivo

Effect of ART1 on the proliferation and migration of mouse colon carcinoma CT26 cells in vivo

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth

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