Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats.

Gustafson-Svärd, Christina; Lilja, Ingela; Hallböök, Olof; Sjödahl, Rune

doi:10.1136/gut.38.1.79

Cited by 103 publications

(47 citation statements)

References 39 publications

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“…Moreover, COX-2 did not appear to contribute to basal prostaglandin synthesis by the colon of normal rats, since administration of the highly selective COX-2 inhibitor, L745,337, had no effect on prostaglandin generation in this situation. Our results are consistent with those of DuBois et al (34) and Gustaffson-Svärd et al (35), who showed COX-1 and COX-2 mRNA expression in the normal rat colon (the latter at low levels). Low or undetectable levels of COX-2 mRNA expression in human colon have also been reported (35)(36)(37).…”

Section: Discussionsupporting

confidence: 83%

“…Our results are consistent with those of DuBois et al (34) and Gustaffson-Svärd et al (35), who showed COX-1 and COX-2 mRNA expression in the normal rat colon (the latter at low levels). Low or undetectable levels of COX-2 mRNA expression in human colon have also been reported (35)(36)(37). Interestingly, elevated expression of COX-2 in the colon has been demonstrated in human colorectal cancer and in experimental models of colonic adenocarcinoma (34)(35)(36)(37).…”

Section: Discussionsupporting

confidence: 83%

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Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2.

Reuter¹,

Asfaha²,

Buret³

et al. 1996

J. Clin. Invest.

401

267

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Cyclooxygenase type 1 is constitutively expressed and accounts for synthesis of prostaglandins in the normal gastrointestinal tract. Cyclooxygenase-2 is expressed at sites of inflammation. Selective inhibitors of cyclooxygenase-2 have been suggested to spare gastrointestinal prostaglandin synthesis, and therefore lack the ulcerogenic effects associated with standard nonsteroidal antiinflammatory drugs. However, the effects of cyclooxygenase-2 inhibitors on inflamed gastrointestinal mucosa have not been examined. We examined cyclooxygenase-2 mRNA and protein expression before and after induction of colitis in the rat, the contribution of cyclooxygenase-2 to colonic prostaglandin synthesis during colitis and the effects of selective inhibitors of cyclooxygenase-2 on colonic injury in this model. Cyclooxygenase-2 mRNA expression increased three to sixfold during the period 24 h to 1 wk after induction of colitis, with marked increases in cyclooxygenase-2 protein expression in the lamina propria and muscularis of the colon during colitis.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 83%

Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2.

Reuter¹,

Asfaha²,

Buret³

et al. 1996

J. Clin. Invest.

401

267

View full text Add to dashboard Cite

show abstract

“…COX-2 also has been linked to colon carcinogenesis (Oshima et al, 1996;Gustafson-Svard et al, 1996), and its overexpression may alter the biologic behavior of tumor cells in various ways Tsuji and DuBois, 1995). Recent studies have suggested that COX-2 regulates metastasis and angiogenesis in colon carcino- Figure 7 Growth-stimulating e ect of exogenous PGE 2 on CE-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation

et al. 2000

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Both nonneoplastic colon epithelium and colon carcinoma cells in situ are continuously exposed to lipopolysaccharide (LPS). Few reports have addressed possible direct e ects of LPS in promotion of colon carcinoma and underlying mechanisms. We found evidence that LPS directly stimulated growth of the human colon carcinoma cell line CE-1 through an increase in the production of prostaglandin E 2 (PGE 2 ) as a result of cyclo-oxygenase-2 (COX-2) expression. LPS induced signi®cant increases in PGE 2 production in CE-1 cells, which were found to express a high-a nity LPS receptor, CD14. Positive correlations were found between PGE 2 production and activation of nuclear factor (NF)-kB as well as expression of both COX-2 mRNA and protein in LPSstimulated CE-1 cells. When CE-1 cells were exposed to exogenous PGE 2 , DNA synthesis increased. These results indicate that LPS may stimulate DNA synthesis in certain colon carcinoma cells as a result of PGE 2 production involving increased COX-2 expression that might result in turn from activation of NF-kB by LPS. Further investigation of the pathways mediating LPSinduced stimulation of colon carcinoma cells may provide insights into LPS e ects in in vivo tumor biology.

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“…Exogenous PGE 2 stimulates proliferation of both human colon cancer cell lines and normal mouse colonocytes (Qiao et al, 1995), and PGE 2 levels are increased in human carcinomas compared with normal colonic mucosa (Rigas et al, 1993). Expression of COX-2 (but not COX-1) is up-regulated in human colorectal adenomas and carcinomas (Eberhart et al, 1994;Kargman et al, 1995;Sano et al, 1995;Gustafson-Svard et al, 1996;Kutchera et al, 1996) and overexpression of COX-2 in rat intestinal epithelial cells is associated with a malignant phenotype (Tsuji and DuBois, 1995). Furthermore, it has recently been reported that administration of a specific COX-2 inhibitor prevents azoxymethane-induced colon carcinogenesis in rats (Kawamori et al, 1998).…”

mentioning

confidence: 99%

Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice

et al. 1999

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Summary Expression of cyclooxygenase 2 (COX-2) is believed to play an important role in adenoma formation in murine polyposis models, and inhibition of COX-2 activity may, at least, partly explain the chemopreventative activity of non-steroidal anti-inflammatory drugs against colorectal cancer in humans. However, the mechanism by which COX-2 acts in intestinal tumorigenesis remains unresolved because of conflicting data on the cellular localization of COX-2 in intestinal mucosa. Using immunohistochemistry with specific COX-2 antiserum, we have shown that COX-2 protein is localized to interstitial cells at the base of and within adenomas of the small and large intestine of multiple intestinal neoplasia (Min) mice. No COX-2 staining was observed in dysplastic epithelial cells within adenomas or in histologically normal epithelium. Moreover, COX-2 staining was observed in lamina propria cells of histologically normal intestine of Min mice. No staining was demonstrated in wild-type littermates. The rat monoclonal antibody F4/80 was used to show that COX-2-positive cells represented a subset of the macrophage population present in the intestine of Min mice. Localization of COX-2 to macrophages implies a paracrine effect of COX-2 function on epithelial cells in adenomas and also on histologically normal epithelium. Up-regulation of COX-2 expression in lamina propria macrophages may precede loss of the second functional Apc allele in epithelial cells before adenoma formation in the Min mouse model of intestinal tumorigenesis.

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Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats.

Cited by 103 publications

References 39 publications

Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2.

Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2.

Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation

Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice

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