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:10.1201/b16680-4

Cited by 10 publications

(12 citation statements)

References 30 publications

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“…Asting et al focused on defining external cell signaling and transcription factors relating to high COX-2 expression in colon cancer cells. High COX-2 expression has been connected with large differences in gene expression compared with normal colon mucosa and low COX-2 expression cells [32]. This observation indicates an association of the extracellular environment with the impact on activation of the intracellular pathway and is in concordance with the theory of dietary factors.…”

Section: Discussionsupporting

confidence: 67%

Is there a place for practical chemoprevention of colorectal cancer in light of COX-2 heterogeneity?

Lewitowicz¹,

Kozieł²,

Głuszek³

et al. 2014

pjp

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COX-2 overexpression is widely recognized as an accidental and relatively important factor in the progress of colon neoplasia, but the practical significance of it has not yet been defined. As such, the purposes of the study were: an analysis of the changes of COX-2 expression within colon adenomas in the dependence of progress of dysplastic level within colon adenomas, the analysis of COX-2 expression in cryptal and superficial parts of polyp and, additionally, the analysis of the COX-2 heterogeneity between colon adenomas. One hundred and four cases with completely resected adenomas with high-grade epithelial dysplasia were included in the research. Each polyp had persistent lowgrade dysplasia and normal colon mucosa at the base as an internal control. Immunohistochemical analysis with monoclonal COX-2 antibody was performed. Regression of COX-2 expression in high-grade colon intraepithelial lesions (HGCoIN) compared with low-grade colon intraepithelial lesions (LGCoIN) (p = 0.00001) was observed. No correlation between stromal COX-2 expression and either LGCoIN or HGCoIN was found (p > 0.05). The next important observation was a difference in superficial and cryptal COX-2 expression (p < 0.001) and the evident heterogeneity of COX-2 expression among adenomas at LGCoIN as well HGCoIN foci (p < 0.01). The regression of COX-2 expression in high-grade parts of adenomas which we described may result in a reduction of the role of chemoprevention by the use of NSAIDs.

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Section: Discussionsupporting

confidence: 67%

Is there a place for practical chemoprevention of colorectal cancer in light of COX-2 heterogeneity?

Lewitowicz¹,

Kozieł²,

Głuszek³

et al. 2014

pjp

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“…We did not observe promoter CpG hypermethylation in the mut p53 and COX-2 gene as it is not frequently regulated via promoter CpG methylation. Moreover, available reports suggest COX-2 promoter CpG methylation is not a frequently occurring phenomenon in cancer [28]. At the protein level, we observed over expression of COX-2 after DMBA / TPA exposure in time dependent manner.…”

Section: Original Research Article 66supporting

confidence: 52%

Recent trends and advances in hemophilia – its management and new therapeutic outcomes

Prasant¹

2014

IJPBR

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Chemoprevention by naturally occurring agents is gaining much attention as a newer dimension in the management of cancer. Many naturally occurring agents have shown cancer chemopreventive potential in a variety of bioassay systems and animal models, having relevance to human disease. Phytic acid or Inositol hexaphosphate (IP6), an antioxidant, is a naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer activity in several experimental models. We assessed the protective effects of Phytic acid against the 7, 12-dimethylbenz [a] anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse skin tumorigenesis at 4 and 16 weeks, the time before and after the tumor development. At molecular level we studied expression and promoter CpG methylation status of p21, DAPK1 and COX-2. Our data suggests exposure of DMBA/TPA methylated the promoter region of p21 and DAPK1 genes in time dependent manner that could be the cause of down regulation of their expression with time, which were reversed by administration of phytic acid. But we did not observe methylation in COX-2 whereas upregulation of COX-2 was observed at protein level in mice treated with DMBA followed by TPA in time dependent manner. Administration of phytic acid prevented theses DMBA/TPA induced molecular changes. Study provides a rationale for cancer chemoprevention by natural occurring compounds like Phytic acid.

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“…Since PGE2 is a downstream product of COX-2, it is possible to assume that the expression of COX-2 may affect the levels of PGE2. A previous study by the present authors proposed FosB as an important transcription factor in CRC patients with high COX-2 tumor tissue expression, since FosB was overexpressed in these patients, comparing with patients who exhibited low COX-2 expression (19). FosB is a member of the AP-1 complex, which has been linked to malignant transformation in several types of cancer, and its components, including FosB, have important roles on cell proliferation (among other functions), which suggests their involvement in cancer development (27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies by the present authors revealed that tumor tissues from CRC patients with high COX-2 expression levels displayed upregulation of several transcription factors, among which, the most overexpressed one was FBJ murine osteosarcoma viral oncogene homolog B (FosB) (19). This transcription factor is implicated in the activator protein-1 (AP-1)/COX-2/PGE2 axis, and may play a relevant role in patients with high expression levels of COX-2.…”

Section: Introductionmentioning

confidence: 91%

“…As NSAIDs have been regarded as potential chemopreventive and/or adjuvant agents for cancer treatment, particularly in CRC patients (19), due to their inhibitory effect on COX enzymes, it is important to understand the mechanisms by which these enzymes exert their actions in the process of carcinogenesis. The development of more effective therapies using combinations of NSAIDs and other inhibitors of the PG pathways depend on a deeper knowledge in this matter.…”

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confidence: 99%

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FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

2017

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Abstract. The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2) content have been associated with poor prognosis in patients with colorectal cancer (CRC). There is a strong correlation between COX-2 expression and PGE2 production in tissues from CRC patients, suggesting an important role for COX-2 on the regulation of PGE2 production. Previous studies by the present authors, where CRC patients were divided into high-or low-COX-2 expressing tumors, displayed important differences in the expression levels of several transcription factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral oncogene homolog B (FosB), which is a member of the activator protein-1 complex, was the highest upregulated transcription factor in patients with high expression levels of COX-2. The present study aimed to investigate the role of FosB on the COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later the messenger (m)RNA expression levels of COX-1 and COX-2, as well as the PGE2 content, were measured. The results indicated that FosB knockdown decreased the expression levels of COX-2 but did not affect the PGE2 content or the mRNA expression levels of COX-1. The present findings suggest an important role for FosB on the regulation of COX-2 expression, but no effect on the regulation of the PGE2 levels. In addition, the present results imply independent regulatory mechanisms for COX-2 expression and PGE2 content.

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COX-2 Gene Expression in Colon Cancer Tissue Related to Regulating Factors and Promoter Methylation Status

Cited by 10 publications

References 30 publications

Is there a place for practical chemoprevention of colorectal cancer in light of COX-2 heterogeneity?

Is there a place for practical chemoprevention of colorectal cancer in light of COX-2 heterogeneity?

Recent trends and advances in hemophilia – its management and new therapeutic outcomes

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

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