Cyclooxygenase Gene Expression in Inflammation and Angiogenesis<sup>a</sup>

Hla, Timothy; Ristimäki, Ari; Appleby, Susan; Barriocanal, Javier Garcia

doi:10.1111/j.1749-6632.1993.tb17152.x

Cited by 151 publications

(57 citation statements)

References 34 publications

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“…One possibility follows that over-expression of COX-2 leads to high levels of prostaglandins synthesis in the tissues. Prostaglandins produced by COX-2 may subsequently facilitate tumor progression by acting as growth factors, differentiation factors, immunosuppressors and angiogenic agents [26,27] . Other possibilities from recent studies indicate that reactive oxygen species (ROS) are generated during the conversion from prostaglandins G2 to prostaglandins H2 [28,29] , this enhanced level of ROS parallels the levels of COX-2 mRNA.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett’s esophagus to adenocarcinoma

Li¹

2006

WJG

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AIM:To investigate the expression of cyclooxygenase-2 (COX-2) and epithelial growth factor receptor (EGFR) throughout the progression of Barrett's esophagus (BE). METHODS:COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS:The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma (EAC). A positive correlation was found between COX-2 expression and EGFR expression.COnCLUSIOn: COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett’s esophagus to adenocarcinoma

Li¹

2006

WJG

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“…Following their synthesis, these prostanoids are secreted and bind to G protein-coupled membrane receptors in target cells in an autocrine or paracrine fashion, thereby triggering downstream signaling events (21). Prostaglandins are important regulators of numerous cellular processes including cell proliferation, inflammation, and angiogenesis (22).…”

Section: Nfatmentioning

confidence: 99%

NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2

Yiu

Toker

2006

Journal of Biological Chemistry

142

135

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The NFAT (nuclear factor of activated T cells) family of transcription factors plays a fundamental role in the transcriptional regulation of the immune response. However, NFATs are ubiquitously expressed, and recent evidence points to their important functions in human epithelial cells and carcinomas. Specifically, NFAT has been shown to be active in human breast and colon carcinoma cells and to promote their invasion through Matrigel. The mechanisms by which NFAT promotes invasion have not been defined. To identify NFAT target genes that induce carcinoma invasion, we have established stable breast cancer cell lines that inducibly express transcriptionally active NFAT. Gene expression profiling by cDNA microarray of cells induced to express NFAT revealed up-regulation of cyclooxygenase-2 (COX-2). Increased NFAT expression and activity induced COX-2 expression as well as prostaglandin E 2 synthesis. This induction was more prominent when NFAT was activated by phorbol 12-myristate 13-acetate and calcium ionophore ionomycin and was blocked by the NFAT antagonist cyclosporin A. Breast cancer cells with elevated COX-2 expression showed increased invasion through Matrigel, and this was reduced in cells treated with COX-2 inhibitors. Conversely, loss of NFAT1 protein expression using small interfering RNA led to a reduction in COX-2 transcription and reduced invasion. Similarly, Matrigel invasion was reduced in cells in which COX-2 expression was reduced using specific siRNA. These findings demonstrate that NFAT promotes breast cancer cell invasion through the induction of COX-2 and the synthesis of prostaglandins.

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“…The constitutively expressed cyclooxygenase-1 (PTGS1, previously known as COX1) isoform appears to regulate many normal physiological functions in several cell types, whereas the inducible isoform, cyclooxygenase-2 (PTGS2, previously COX2), is usually expressed at low levels in most tissues and cells, but is significantly induced by a wide range of inflammatory stimuli such as lipopolysaccharide, cytokines and chemicals [1,2]. PTGS2 overexpression has been demonstrated in several human inflammatory diseases [2]. In the pancreatic islet PTGS2 is constitutively and dominantly expressed [7,8] and here PTGS2 products such as prostaglandin E 2 (PGE 2 ) are believed to play a role in inflammation, islet destruction and inhibition of insulin secretion [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Cyclooxygenase (PTGS, previously known as COX) enzymes catalyse the rate-limiting step in the conversion of arachidonic acid to prostaglandins [1][2][3][4][5], which are important mediators of acute and chronic inflammation, development and immune functions [6]. The constitutively expressed cyclooxygenase-1 (PTGS1, previously known as COX1) isoform appears to regulate many normal physiological functions in several cell types, whereas the inducible isoform, cyclooxygenase-2 (PTGS2, previously COX2), is usually expressed at low levels in most tissues and cells, but is significantly induced by a wide range of inflammatory stimuli such as lipopolysaccharide, cytokines and chemicals [1,2].…”

Section: Introductionmentioning

confidence: 99%

Increased expression of cyclooxygenase-2 in human pancreatic islets treated with high glucose or ligands of the advanced glycation endproduct-specific receptor (AGER), and in islets from diabetic mice

et al. 2005

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Aims/hypothesis: The cyclooxygenase-2 (PTGS2, previously known as COX2) enzyme and its products, such as prostaglandin E 2 (PGE 2 ), have been implicated in the pathogenesis of several inflammatory diseases including islet dysfunction under diabetic conditions. In this study we evaluated whether diabetic conditions in vitro, such as highglucose (HG) culture or AGE, or in vivo in animal models of diabetes can induce PTGS2 expression and activity in pancreatic islets. Materials and methods: Isolated human pancreatic islets were treated for 24 h with HG (25 mmol/l) or with S100b (5 mg/l), a specific ligand for the AGEspecific receptor. PTGS2 and cyclooxygenase-1 (PTGS1, previously known as COX1) mRNA, protein expression and product PGE 2 were analysed by RT-PCR, Western blots and specific enzyme immunoassay respectively. Islet PTGS2 production in animal models was assessed by immunofluorescence. Results: Treatment of human pancreatic islets with HG and S100b led to a three-five-fold induction of PTGS2 mRNA (p<0.001). PTGS2 protein and its product PGE 2 (351.4±13.05 fg/ml vs control 39.4±0.11 fg/ml) were also increased (p<0.001). Pretreatment with specific inhibitors demonstrated the involvement of protein kinase C and oxidant stress in S100b-and HG-induced PTGS2 expression. However, insulin secretion was not significantly altered by S100b. Double immunofluorescent staining showed increased PTGS2 production in pancreatic islets from diabetic mice relative to corresponding controls. Conclusion/ interpretation: These results show for the first time that diabetes as well as diabetic conditions such as AGE and HG in vitro can directly upregulate the expression of the inflammatory PTGS2 gene in pancreatic islets. This might contribute to the pathogenesis of islet dysfunction in diabetes.

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Cyclooxygenase Gene Expression in Inflammation and Angiogenesis^a

Cited by 151 publications

References 34 publications

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett’s esophagus to adenocarcinoma

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett’s esophagus to adenocarcinoma

NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2

Increased expression of cyclooxygenase-2 in human pancreatic islets treated with high glucose or ligands of the advanced glycation endproduct-specific receptor (AGER), and in islets from diabetic mice

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Cyclooxygenase Gene Expression in Inflammation and Angiogenesisa

Cited by 151 publications

References 34 publications

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett’s esophagus to adenocarcinoma

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett’s esophagus to adenocarcinoma

NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2

Increased expression of cyclooxygenase-2 in human pancreatic islets treated with high glucose or ligands of the advanced glycation endproduct-specific receptor (AGER), and in islets from diabetic mice

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Cyclooxygenase Gene Expression in Inflammation and Angiogenesis^a