Cyclooxygenase-2 and its role in colorectal cancer development

Wendum, Dominique; Masliah, J.; Trugnan, Germain; Fléjou, Jean‐François

doi:10.1007/s00428-004-1105-2

Cited by 81 publications

(60 citation statements)

References 65 publications

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“…Notably, the neutrophils that accumulated in vivo in areas of p120 ablation were unusual in that they expressed very high levels of COX-2 ( Figure 7, B and C), an enzyme closely associated with IBD (40,43) and colon cancer (44). Therefore, we examined whether COX-2 levels were influenced by p120 KD in vitro.…”

Section: Figurementioning

confidence: 99%

“…Of note, most neutrophils in the p120 KO colon were also COX-2 positive. Elevated COX-2 activity is thought to play an important role in both IBD and colon cancer (41,43,44), but the source of the activity is controversial. Elevated COX-2 has been reported variously in epithelial cells, as well as almost every stromal cell type (44, 64) -macrophages in particular (65).…”

Section: Figurementioning

confidence: 99%

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p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Smalley-Freed¹,

Ефимов²,

Burnett³

et al. 2010

J. Clin. Invest.

123

152

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Epithelial-cadherin (E-cadherin) is a master organizer of the epithelial phenotype. Its function is regulated in part by p120-catenin (referred to herein as p120), a cytoplasmic binding partner that directly regulates cadherin stability. As it has been suggested that cadherins have a role in inflammatory bowel disease (IBD), we sought to investigate this further by assessing the effect of p120 deficiency in mouse small intestine and colon. p120 conditional KO mice were superficially normal at birth but declined rapidly and died within 21 days. Cellcell adhesion defects and inflammation led to progressive mucosal erosion and terminal bleeding, similar to what is observed in a dominant-negative cadherin mouse model of IBD. Additionally, selective loss of adherens junctions and accumulation of atypical COX-2-expressing neutrophils in p120-null areas of the colon were observed. To elucidate the mechanism, direct effects of p120 deficiency were assessed in vitro in a polarizing colon cancer cell line. Notably, transepithelial electrical resistance was dramatically reduced, neutrophil binding was increased 30 fold, and levels of COX-2, an enzyme associated with IBD, were markedly increased in neutrophils. Our data suggest that p120 loss disrupts the neonatal intestinal barrier and amplifies neutrophil engagement and that these changes lead to catastrophic inflammation during colonization of the neonatal gut with bacteria and other luminal antigens. Thus, we conclude that p120 has an essential role in barrier function and epithelial homeostasis and survival in the intestine.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Smalley-Freed¹,

Ефимов²,

Burnett³

et al. 2010

J. Clin. Invest.

123

152

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“…IGF-1 treatment dramatically increases COX-2 expression and PGE 2 levels, but not COX-1 expression in the cells. Recent studies show that high levels of COX-2 and PGE 2 expression are associated with cancer progression and angiogenesis in other human cancers such as colon, gastric, and breast cancers (12,15,31,32). Since IGF-I and its receptor IGF-IR are frequently overexpressed in human ovarian cancer (2)(3)(4), the induction of COX-2 expression by IGF-I may play an important role in the angiogenesis switch during ovarian cancer development and progression.…”

Section: Discussionmentioning

confidence: 99%

“…COX-2 expression can be induced by inflammatory cytokines and by growth factors (15). COX-2 expression can also be induced by activation of oncogenes and inactivation of tumor suppressor genes (15).…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells☆

Cao

Liu

Dixon

et al. 2007

Cellular Signalling

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Elevated levels of insulin-like growth factor-I (IGF-I) are associated with ovarian carcinogenesis and progression. However, the molecular mechanisms by which IGF-I contributes to ovarian cancer development remain to be elucidated. Cyclooxygenase-2 (COX-2) is a crucial player in the pathogenesis of human malignancies. Herein we showed that IGF-I efficiently induced COX-2 expression and PGE 2 biosynthesis at physiologically relevant concentrations in human ovarian cancer cells. IGF-I treatment significantly increased COX-2 transcriptional activation. IGF-I also stabilized COX-2 mRNA through the COX-2 3′-untranslated region (3′-UTR), which appeared independent of the conserved AU-rich elements. We next investigated the signaling pathways involved in IGF-I-induced COX-2 expression. We found that PI3K inhibitor wortmannin or LY294002 blocked COX-2 expression induced by IGF-I. Wortmannin treatment or a dominant negative PI3K mutant significantly inhibited IGF-I-induced COX-2 mRNA stabilization, but only slightly decreased COX-2 transcriptional activation. We showed that ERK1/2 and p38 MAPKs were required for IGF-I-induced COX-2 expression and that activation of both pathways by IGF-I increased COX-2 transcriptional activation and its mRNA stability. IGF-I stimulated PKC activation in the cells and pretreatment with PKC inhibitor bisindolylmaleimide prevented IGF-I-induced COX-2 transcriptional activation and mRNA stabilization, and inhibited COX-2 mRNA and protein expression. Taken together, our data demonstrate that IGF-I induces COX-2 expression in human ovarian cancer cells, which is mediated by three parallel signaling cascades -PI3K, MAPK, and PKC pathways that differentially regulate COX-2 expression at transcriptional and posttranscriptional levels.

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“…Additionally, we analyzed the lipid composition of liver tissue and colonic mucosa and measured the serum concentrations of total cholesterol and triglyceride to understand the possible mechanisms by which CPO could modify the occurrence of the lesions. Since overexpression of cyclooxygenase-2 (COX-2) is involved in colon carcinogenesis and certain cyclooxygenase inhibitors are likely to be useful as colon cancer chemopreventive agents (23)(24)(25)(26), the effects of CPO on the expression of COX-2 in the non-lesional colonic mucosa were investigated. Also, biomarkers such as proliferating cell nuclear antigen (PCNA)-labeling index and apoptotic index were measured immunohistochemically in colonic mucosa, since BMO exerted an inhibitory effect on ACF via reduction of the PCNA index and induction of apoptosis in our previous study (20).…”

Section: Introductionmentioning

confidence: 99%

Catalpa seed oil rich in 9t,11t,13c-conjugated linolenic acid suppresses the development of colonic aberrant crypt foci induced by azoxymethane in rats

Suzuki

Yasui²,

Kohno³

et al. 2006

Oncol Rep

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Abstract. Catalpa (Catalpa ovata) seed oil (CPO) is a unique oil that contains a high amount of 9trans,11trans,13cis-conjugated linolenic acid. In the present study, we investigated whether dietary administration with CPO affects the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats to elucidate its possible cancer chemopreventive efficiency. Also, the effect of CPO on the fatty acid composition of liver tissue and colonic mucosa, the serum levels of total cholesterol and triglyceride, and the mRNA expression of cyclooxygenase (COX)-2 in the colonic mucosa were measured. In addition, the cell proliferation activity and apoptotic index in the colonic mucosa were estimated immunohistochemically. Animals were given two weekly subcutaneous injections of AOM (20 mg/kg body weight). They also received the experimental diet containing 0.01%, 0.1% or 1% CPO for 4 weeks, starting one week before the first dosing of AOM. AOM exposure produced a substantial number of ACF (99±28) at the end of the study (week 4). Dietary administration of CPO reduced the number of ACF (AOM + 0.01% CPO, 32±11, P<0.001; AOM + 0.1% CPO, 35±18, P<0.001; AOM + 1% CPO, 18±10, P<0.001). 9t,11t-conjugated linoleic acid was detected in the liver tissue and colonic mucosa of rats fed the CPO-containing diet. Additionally, dietary administration with CPO decreased the serum triglyceride level and the expression of COX-2 mRNA in the colonic mucosa. The indices of cell proliferation and apoptosis in the colonic mucosa of rats treated with AOM and 1% CPO have significant differences when compared with the AOM alone group. These findings suggest the possible chemopreventive activity of CPO in the early phase of colon carcinogenesis.

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Cyclooxygenase-2 and its role in colorectal cancer development

Cited by 81 publications

References 65 publications

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells☆

Catalpa seed oil rich in 9t,11t,13c-conjugated linolenic acid suppresses the development of colonic aberrant crypt foci induced by azoxymethane in rats

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