Increased Expression of Cyclooxygenase-2 to -1 in Human Colorectal Cancers and Adenomas, but not in Hyperplastic Polyps

Maekawa, Masato; Sugano, Kokichi; Sano, Hajime; Miyazaki, Shôzo; Ushiama, Mineko; Fujita, Shin; Gotoda, Takuji; Yokota, Toshiyuki; Ohkura, H; Kakizoe, Tadao; Sekiya, Takao

doi:10.1093/jjco/28.7.421

Cited by 60 publications

(37 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…26 In our study, we found that COX-2 is increased in a subset of colorectal adenocarcinomas. Based on similar results by other groups [27][28][29] as well as on the results of epidemiologic 30,31 and in vitro cell culture studies, inhibitors of COX-2 have been regarded as one of the most promising potential new therapeutic options for malignant tumors. 32,33 These substances have been shown to reduce tumor growth in various in vitro studies as well as in vivo animal experiments.…”

Section: Discussionmentioning

confidence: 69%

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

et al. 2006

View full text Add to dashboard Cite

There is growing body of evidence that post-translational events contribute-in addition to genetic changes-to the progression of malignant tumors. These post-translational alterations may provide targets for new therapeutic approaches. The ELAV-like protein HuR stabilizes a group of cellular mRNAs which contain AU-rich elements in their 3 0 untranslated region. To investigate a possible contribution of post-translational changes to the progression of colon cancer and to overexpression of COX-2, we studied expression of HuR and COX-2 a cohort of colorectal adenocarcinomas and in colon cancer cell lines. All cell lines showed an expression of HuR mRNA and protein. In tumor tissue of colon carcinomas we observed two different staining patterns of HuR: A nuclear expression in 98% as well as an additional cytoplasmic expression in 53% of cases. COX-2 was expressed in 63% of carcinomas. Cytoplasmic expression of HuR was significantly associated with increased COX-2 expression as well as with high tumor stage. In univariate Kaplan-Meier analysis, grading, tumor stage and nodal status but not HuR or COX-2 expression were prognostic factors for overall survival. Our results suggest that the overexpression of HuR in colon cancer may be part of a regulatory pathway that controls the mRNA stability of cyclooxygenase-2 and provides an interesting example for a contribution of a dysregulation of mRNA stability to the progression of colorectal cancer. Based on our results, further studies are necessary to investigate whether HuR might be a potential target for a molecular tumor therapy.

show abstract

Section: Discussionmentioning

confidence: 69%

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Previous studies have implicated COX-2 in oncogenesis in a number of cancers (25)(26)(27), and have demonstrated Table III. Changes in body weight and mortality rate of nude mice with SW1116 xenografts (n=8 per group).…”

Section: Discussionmentioning

confidence: 99%

Sinomenine, a COX-2 inhibitor, induces cell cycle arrest and inhibits growth of human colon carcinoma cells in vitro and in vivo

et al. 2015

View full text Add to dashboard Cite

Abstract. Certain non-steroidal anti-inflammatory drugs may possess anti-tumorigenic effects in certain cancer cell types. Sinomenine (SIN) is an alkaloid from Sinomenium acutum, a Chinese medicinal plant that inhibits inflammatory reactions and that has been used in the treatment of neuralgia and rheumatic diseases. In this study, we investigated the anticancer effects of SIN against colorectal cancer in vitro and in vivo, as well as the underlying mechanisms. The effects of SIN on proliferation, cell cycle progression and cyclooxygenase (COX)-2 expression were examined in human colorectal cancer-derived SW1116 cells. The in vivo effects of SIN were examined in a model of SW1116 tumor xenograft growth in athymic nude mice. Changes in COX-2 expression induced by the biological effects of SIN were analyzed by western blot analysis. The effects of SIN treatment on G1 phase cell cycle regulators in xenografts were analyzed by immunohistochemistry. Our findings demonstrate that SIN inhibits the proliferation of SW1116 cells by promoting their accumulation in the G1 phase, with concomitant suppression of COX-2 expression. Time-and dose-dependent inhibition of tumor growth and reduced toxicity were observed in nude mice administered daily intraperitoneal injections of SIN at doses of 25, 50 and 100 mg/kg. SIN-treated tumors also exhibited reduced COX-2 expression, a marked increase in Cip1/p21 protein levels and a decrease in the levels of cyclin D1 and cyclin E. SIN may be an effective chemopreventive agent against colorectal cancer. The growth inhibitory properties of SIN against colorectal cancer may be mediated via a COX-2 inhibitory effect and cell cycle arrest in the G1 phase.

show abstract

“…24,25 'PTGER1 (prostaglandin E receptor 1 (subtype EP1), 42 kDa)' is activated by COX-2/PGE-2 signaling that is overexpressed in 90% of sporadic colon carcinomas and is induced by hypoxia. 78,79 Another target that has shown to directly upregulate COX-2 expression is the 'HIST1H1A (histone cluster 1, H1a)', whose overexpression had been significantly associated with a shorter colorectal cancer-specific and overall survival. 80 Through a SRC-dependent pathway, PTGER1 activates the 'ANGPTL4 (angiopoietin-like 4)' protein that may promote colorectal carcinogenesis.…”

Section: Gene Expression Profiles and Deranged Signaling Pathwaysmentioning

confidence: 99%

Familial colorectal cancer type X: genetic profiles and phenotypic features

Dominguez‐Valentin

Therkildsen²,

Silva³

et al. 2015

Modern Pathology

View full text Add to dashboard Cite

Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.

show abstract

Increased Expression of Cyclooxygenase-2 to -1 in Human Colorectal Cancers and Adenomas, but not in Hyperplastic Polyps

Abstract: The proportion of COX-2 to COX-1 expression was elevated in most human colorectal cancers and adenomas, but not in hyperplastic polyps. Therefore, the increased proportion of COX-2 expression might be an early event in the carcinogenesis of colorectal cancer.

Cited by 60 publications

References 24 publications

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

Sinomenine, a COX-2 inhibitor, induces cell cycle arrest and inhibits growth of human colon carcinoma cells in vitro and in vivo

Familial colorectal cancer type X: genetic profiles and phenotypic features

Contact Info

Product

Resources

About