Characterization of the Genomic Structure, Chromosomal Location and Promoter of Human Prostaglandin H Synthase-2 Gene

Tazawa, Ryushi; Xu, Xiaoming; Wu, Kezuo; Wang, Lee-Ho

doi:10.1006/bbrc.1994.2167

Cited by 258 publications

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“…In model systems, overexpression of the COX-2 protein caused by hypoxia in human umbilical vein endothelial cells and by IL-1 in rheumatoid synoviocytes has been shown to be mediated by NF-kB (Schmedtje et al, 1997;Chen et al, 2000). Furthermore, there are two NF-kB consensus sites present in the promoter region of the human COX-2 gene (Tazawa et al, 1994), these being the NF-kB-3 0 site (À223/À214) and the NF-kB-5 0 site (À447/À438), indicating that NF-kB may be involved in COX-2 induction (Bowie and O'Neill, 2000).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

et al. 2003

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Cyclooxygenase-2 (COX-2) is selectively overexpressed in colorectal tumours. The mechanism of COX-2 induction is not fully understood, but requires de novo messenger RNA and protein synthesis, indicating regulation at the transcriptional level. Sequence analysis of the 5 0 -flanking region of the COX-2 gene shows two nuclear factor-kB (NF-kB) sites. Inhibition of this protein in model cell culture systems attenuates COX-2 expression and implies that NF-kB plays an important role in COX-2 induction. We measured COX-2, NF-kB and IkB kinase a (IKKa) protein expression in matched colonic biopsy samples comprising both nontumour and adjacent tumour tissue from 32 colorectal cancer patients using immunohistochemistry. There was none or very little expression of COX-2, NF-kB and IKKa in non-neoplastic colon epithelial cells, while the expression of all three of these proteins was significantly increased (Po0.05, Wilcoxon's signed rank test) in adjacent cancerous cells. Moreover, all three proteins were found to be coexpressed in the neoplastic epithelium, with the expression of COX-2 and NF-kB highly correlated (Pearson's correlation, Po0.005). There was no apparent correlation between enhanced COX-2, NF-kB or IKKa expression and tumour Dukes' stages. Our results are compatible with the hypothesis that IKKa and NF-kB are involved in COX-2 induction in these tumours and the lack of association between COX-2 expression and severity of disease as measured by Dukes' stage is consistent with the proposal that COX-2 expression is an early postinitiation event.

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Section: Discussionmentioning

confidence: 99%

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

et al. 2003

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“…A major mechanism for the regulation of prostaglandin synthesis occurs at the level of cyclooxygenase, where the first rate-limiting step in the conversion of arachidonic acid to prostaglandins is catalyzed by two isoforms. COX-2 is associated with biological events such as injury, inflammation, and proliferation [8]. COX-2 is normally undetectable in lung tissue, and is induced by cytokines, growth factors, oncogenes and tumour promoters [9].…”

Section: Introductionmentioning

confidence: 99%

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Stražišar

Mlakar

Glavač

2009

Cellular and Molecular Biology Letters

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Abbreviations used: ADC -adenocarcinoma; CDK2 -cyclin-dependent kinase 2; cDNAcomplementary DNA; COX-2 -cyclooxygenase 2; C T -cycle threshold; DNAdeoxyribonucleic acid; GAPDH -glyceraldehyde-3-phosphate dehydrogenase; hTERThuman telomerase reverse transcriptase; IHC -immunohistochemistry; LATS2 -homolog of large tumour suppressor 2, Drosophilae; LCC -large cell carcinoma; MDM2 -mouse double minute 2 homolog; mRNA -messenger RNA; NSCLC -non-small cell lung cancer; p21 -cyclin-dependent kinase inhibitor 1A; p53 -tumour protein p53; PCR -polymerase chain reaction; pTNM -pathological tumour-node-metastasis; RB -retinoblastoma; RNAribonucleic acid; r s -Spearman's rank correlation coefficient; RT-PCR -real time PCR; S100A2 -S100 calcium binding protein A2; SCC -squamous cell carcinoma , we analysed the expression of the COX-2, hTERT, MDM2, LATS2 and S100A2 genes and researched the relationships between the NSCLC types and the differences in expression levels. The differences in the expression levels of the LATS2, S100A2 and hTERT genes in different types of NSCLC are significant. hTERT and COX-2 were over-expressed and LATS2 under-expressed in all NSCLC. We also detected significant relative differences in the expression of LATS2 and MDM2, hTERT and MDM2 in different types of NSCLC. There was a significant difference in the average expression levels in S100A2 for ADC and SCC. Our study shows differences in the expression patterns within the NSCLC group, which may mimic the expression of the individual NSCLC type, and also new relationships in the expression levels for different NSCLC types.

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“…Sequence analysis of the 5 0 -flanking region of the COX-2 gene shows two nuclear factor-kB (NF-kB) sites (Tazawa et al, 1994). In vitro inhibition of this protein has been shown to attenuate COX-2 expression in colorectal cancer cells, indicating that NF-kB may play an important role in COX-2 induction (Plummer et al, 1999;Williams et al, 2003).…”

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confidence: 99%

Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

et al. 2009

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BACKGROUND: Cyclooxygenase-2 (COX-2) is selectively over-expressed in colorectal tumours. The mechanism of COX-2 induction in these tumours is not fully understood, although evidence suggests a possible link between nuclear factor (NF)-kB and COX-2. We hypothesised an association between COX-2 expression and NF-kB-p65, NF-kB-p50 and IkB-kinase-a (IKKa) in both epithelial and stromal cells in human colorectal cancer. METHODS: Using immunohistochemistry, we measured COX-2, NF-kB-p65, NF-kB-p65 nuclear localisation sequence (NLS), NF-kBp50, NF-kB-p50 NLS and IKKa protein expression in matched colorectal biopsy samples comprising both non-tumour and adjacent tumour tissue from 32 patients with colorectal cancer. RESULTS: We have shown that stromal cells of malignant and surrounding normal colorectal tissue express COX-2. In all cell types of malignant tissue, and in vascular endothelial cells (VECs) of neighbouring normal tissue, COX-2 expression was strongly associated with NF-kB-p65 expression (Pearson's correlation, P ¼ 0.019 for macrophages, P ¼ 0.001 for VECs, P ¼ 0.002 for fibroblasts (malignant tissue), and P ¼ 0.011 for VECs (non-malignant tissue)) but not NF-kB-p50 or IKKa. CONCLUSIONS: These data suggest that in these cells COX-2 induction may be mediated through activation of the canonical NF-kB pathway. Finally, the lack of association between COX-2, NF-kB-p65 or IKKa in stromal cells with the clinical severity of colorectal cancer as determined by Duke's stage, suggests that COX-2, NF-kB-p65 and IKKa expression are possibly early post-initiation events, which could be involved in tumour progression.

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Characterization of the Genomic Structure, Chromosomal Location and Promoter of Human Prostaglandin H Synthase-2 Gene

Cited by 258 publications

References 0 publications

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

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