Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells

Kinoshita, Takahiro; Takahashi, Yoshitaka; Sakashita, Toshiki; Inoue, H.; Tanabe, Tadashi; Yoshimoto, Tanihiro

doi:10.1016/s1388-1981(99)00034-7

Cited by 90 publications

(65 citation statements)

References 36 publications

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“…25 An involvement of COX-1, comparable with that of the COX-2 isoform, in intestinal tumorigenesis in Min mice was also demonstrated on the basis of a genetic approach by Chulada et al 14 We confirmed this using a pharmacologic approach with mofezolac against AOM-induced colonic ACFs in rats and intestinal polyps in APC1309 mice. 15 PGE 2 levels in polyps are increased compared with those of the normal tissue and suppressed by COX-1 or COX-2 deficiency.…”

Section: Discussionsupporting

confidence: 67%

Combined effects of cyclooxygenase‐1 and cyclooxygenase‐2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice

Kitamura¹,

Itoh

Noda

et al. 2004

Intl Journal of Cancer

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As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm mofezolac plus 200 ppm nimesulide, 600 ppm mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis. © 2004 Wiley-Liss, Inc. Key words: Apc knockout mice; COX-1 selective inhibitor; COX-2 selective inhibitor; intestinal tumorigenesis; combined effectLong-term use of aspirin, a nonsteroidal antiinflammatory drug (NSAID), has been found in the epidemiologic studies to result in reduction in mortality rate from colorectal cancer. 1,2 Furthermore, treatment with NSAIDs suppresses the development of chemical carcinogen-induced colon cancers in experimental animals. 3,4 Similarly, decrease has been achieved with such agents regarding intestinal polyps in patients with familial adenomatous polyposis (FAP) [5][6][7] and in an animal model of the disease, mutant mice with a truncated adenomatous polyposis coli (Apc) gene. 8 NSAIDs block arachidonic acid metabolism by inhibiting cyclooxygenase (COX) activity and thus reducing levels of prostaglandins, which affect cell proliferation, tumor growth, apoptosis and immune responsiveness. Two enzyme isoforms of COX are known, referred to as COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and plays a role in various physiologic functions, while COX-2 is transiently inducible by stimuli such as cytokines, growth factors and hormones and contributes to inflammation. 9 By using COX-2 selective inhibitors or mutant mice featuring disruption of the gene encoding this enzyme, relevance to carcinogenesis in various organs, including the colon, has been shown. 10 -13 Possible involvement of COX-1 in colon carcinogenesis has also been reported. Genetic disruption of the COX-1 gene decreased the number of intestinal polyps in ...

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Section: Discussionsupporting

confidence: 67%

Combined effects of cyclooxygenase‐1 and cyclooxygenase‐2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice

Kitamura¹,

Itoh

Noda

et al. 2004

Intl Journal of Cancer

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“…Although the exact mechanisms by which celecoxib suppresses β-catenin-accumulated crypts remains to be elucidated, accumulating evidence suggests that overexpression of COX-2 may induce growth stimulation in colon cancer cells. 29,30) We have demonstrated that celecoxib significantly decreases proliferative activity in β-catenin-accumulated crypts. Our results may suggest that celecoxib inhibits the proliferative activity of cellular population in premalignant lesions through inhibition of the increased COX-2 activity in such early appearing lesions.…”

Section: Discussionmentioning

confidence: 98%

Suppression of Occurrence and Advancement of β‐Catenin‐accumulated Crypts, Possible Premalignant Lesions of Colon Cancer, by Selective Cyclooxygenase‐2 Inhibitor, Celecoxib

Yamada

Yoshimi

Hirose

et al. 2001

Japanese Journal of Cancer Research

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Suppression of occurrence and advancement of premalignant lesions is important for cancer prevention. Our previous studies clarified that β β β β-catenin-accumulated crypts, independent of aberrant crypt foci (ACF), are probably direct precursors of colon cancers in rats. Here we investigated the effects of a selective cyclooxygenase-2 inhibitor, celecoxib, on the development of β β β β-cateninaccumulated crypts in comparison with those on ACF. Male F344 rats were divided into 4 groups. Groups 1-3 were administered azoxymethane (AOM) s.c. at a dose of 15 mg/kg body weight, once weekly for 3 weeks to induce β β β β-catenin-accumulated crypts. Groups 2 and 3 also received experimental diet containing celecoxib (500 and 1500 ppm, respectively) for 8 weeks, starting a week before the first dosing of AOM. At termination, the frequency and crypt multiplicity (number of crypts/lesion) of β β β β-catenin-accumulated crypts of groups 2 and 3 were significantly less than that of group 1. Furthermore, numbers of silver-stained nucleolar organizer regions (AgNORs)/nucleus in β β β β-catenin-accumulated crypts were also decreased by exposure to celecoxib. In this study, celecoxib had greater effects on the frequency and growth of β β β β-catenin-accumulated crypts than on those of ACF. These findings represent additional evidence that β β β β-catenin-accumulated crypts are premalignant lesions of colon cancer. The results also suggest that β β β β-catenin-accumulated crypts could be a novel target for evaluation of possible chemopreventive agents against colon carcinogenesis, and indicate that possible chemopreventive effects of celecoxib on the initial stage of colon carcinogenesis may be related to modulation of cell proliferation activity in such early lesions.

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“…Consistent with this e ect, expression of COX-2 has been evaluated in di erent types of human malignancies and COX-2 levels are increased in intestinal adenomas and adenocarcinomas compared to matched normal mucosa (Eberhart et al, 1994;Williams et al, 1996). Expression of COX-2 in cultured cells confers a resistance to undergo programmed cell death Tsujii and DuBois, 1995), promotes angiogenesis Williams et al, 2000a), stimulates metastatic potential (Tsujii et al, 1997) and modulates proliferation (Kinoshita et al, 1999). Inactivation of the COX-2 gene in mice is associated with decreased formation of intestinal adenomas (Oshima et al, 1996) with similar e ects being seen in prostaglandin E receptor (EP 1 ) knockout mice (Watanabe et al, 1999).…”

Section: Introductionmentioning

confidence: 83%

Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor

Zhang

DuBois

2001

Oncogene

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Numerous reports suggest that use of nonsteroidal anti-in¯ammatory drugs (NSAIDs) decrease mortality from colorectal cancer. To better understand all of the mechanisms underlying this e ect, the global pattern of gene expression in colon carcinoma cells following treatment with NS-398, a selective cyclooxygenase-2 inhibitor was evaluated. We utilized suppression subtractive hybridization combined with di erential screening to identify genes whose expression was a ected following treatment. Among the subtracted cDNA fragments con®rmed as di erentially expressed, there were two which are known to be involved in the regulation of cell adhesion (human FAT and proto-cadherin-7). We identi®ed two other genes whose levels were decreased and these are known to be involved in the regulation of cell proliferation (cyclin K and p-100). We identi®ed additional genes which are involved in di erent signaling pathways which regulate programmed cell death (Dynamin 2, Pdcd4 and LIP.1). These results provide evidence that some of the e ects of NS-398 on carcinoma cells may be due to modulation of genes which regulate programmed cell death, cell proliferation and cell ± cell communication. Additional studies are underway to determine the biological function of the novel genes that were identi®ed. Oncogene (2001) 20, 4450 ± 4456.

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Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells

Cited by 90 publications

References 36 publications

Combined effects of cyclooxygenase‐1 and cyclooxygenase‐2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice

Combined effects of cyclooxygenase‐1 and cyclooxygenase‐2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice

Suppression of Occurrence and Advancement of β‐Catenin‐accumulated Crypts, Possible Premalignant Lesions of Colon Cancer, by Selective Cyclooxygenase‐2 Inhibitor, Celecoxib

Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor

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