| Description | COX2 is an enzyme that belongs to the prostaglandin G/H synthase family. It consists of 604 amino acids and has a molecular weight of 68996Da.
COX2 possesses two catalytic activities and respective active sites:
a cyclooxygenase (COX) that converts arachidonic acid to a prostaglandin endoperoxide, prostaglandin G2 (PGG2), and a peroxidase (POX) that reduces PGG2 to PGH2.
COX2 functions as homodimer although each subunit has both a POX and a COX active site.
Each subunit binds one heme B (iron-protoporphyrin IX) group. |
| Expression | Wide expression in alimentary system (esophagus, pharynx), male reproductive system (prostate, seminal vesicles, ejaculatory duct), female reproductive system (cervix, uterus), hematopoietic system (bone marrow, monocytes). |
| Localisation | Intracellular, cytoplasm, microsome, microsomal membrane. |
| Function | Enzyme that functions both as a dioxygenase and as a peroxidase. COX-2 catalyzes the transformation of arachidonic acid to prostaglandin H2, which is the rate-limiting step in the formation of prostaglandins (PGs) and thromboxane A2 (TXA2). COX-2 is a potent mediator of inflammation and is implicated in prostanoid signaling in activity dependent plasticity. It is an inducible enzyme that plays an important role in several pathophysiological processes, including inflammation, angiogenesis, and tumorigenesis. |
| Entity | Colorectal Cancers |
| Disease | COX2 is involved in regulation of apoptosis, proliferation and invasiveness of colorectal tumor cells and promotes angiogenesis in several animal colon cancer models. It is also implicated in several premalignant lesions including adenomatous polyps. COX2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2. |
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| Entity | Gastric Cancer |
| Disease | Expression of COX2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis. |
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| Entity | Non small cell lung cancer |
| Disease | Non-small-cell lung cancer (NSCLC), especially adenocarcinomas, overexpress COX2, which contributes to the progression of malignancy by several mechanisms. |
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| Entity | Cholangiocarcinoma |
| Disease | COX2 has been implicated in cholangiocarcinogenesis. Selective COX-2 inhibitors have been shown to inhibit cholangiocarcinoma cell growth in vitro and in animal models. |
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| Entity | Uterine Carcinosarcoma |
| Disease | COX2 is overexpressed in one-third of uterine carcinosarcomas. COX-2 expression is a strong indicator of unfavorable prognosis. |
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| Entity | Head and Neck squamous cell cancer |
| Disease | COX2 is overexpressed in a variety of premalignant and malignant conditions, including oral leukoplakia and squamous cell carcinoma of the head and neck. |
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| Entity | Ovarian cancer |
| Disease | COX-2 is increased in epithelial ovarian cancer and PGE2-synthesis and signalling are important for malignant transformation and progression. |
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| Entity | Pancreatic cancer |
| Disease | Mounting evidence suggests that COX2 is implicated in pancreatic cancer.
Immunohistochemical, RT-PCR, and Western blotting studies have shown that COX2, is upregulated in human pancreatic cancer cell lines as well as human pancreatic cancer tissues compared with normal ductal cells and normal pancreas specimens. COX2 inhibitors significantly inhibit pancreatic cancer growth both in vitro and in vivo while simultaneously induce apoptosis. |
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| Entity | Other Malignant Diseases |
| Disease | Similar to above tumors, COX2 is implicated in carcinogenesis of multiple tumors including transitional cell bladder cancer, prostate cancer, uterine cancer, cervical cancer, angiosarcoma, hepatocellular cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, thyroid cancer, Wilms tumor. |
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| Entity | Primary Dysmenorrhea |
| Disease | In vivo studies have demonstrated that selective COX-2 inhibitors are effective in treatment of primary dysmenorrhea in women. |
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| Entity | Inflammatory Conditions |
| Disease | COX2 occupies an important in several inflammatory diseases such as osteoarthritis and rheumatoid arthritis. |
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| Entity | Neurolomuscular Disorders |
| Disease | COX2 is implicated in encephalitis, cerebral infarction, polyneuropathy and muscular dystrophies. |
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| Entity | Cardiovascular toxicity and thromboembolic Discorders |
| Note | Selective inhibition of COX2 (without concomitant inhibition of COX1) is associated with significant cardiovascular risk and thromboembolic phenomena. |
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| Entity | Retinopathy |
| Disease | COX2 plays an important role in ischemic proliferative retinopathy, as in the case of diabetic retinopathy. |
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| Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. |
| Lin DT, Subbaramaiah K, Shah JP, Dannenberg AJ, Boyle JO |
| Head & neck. 2002 ; 24 (8) : 792-799. |
| PMID 12203806 |
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| Dynamic regulation of cyclooxygenase-2 promoter activity by isoforms of CCAAT/enhancer-binding proteins. |
| Zhu Y, Saunders MA, Yeh H, Deng WG, Wu KK |
| The Journal of biological chemistry. 2002 ; 277 (9) : 6923-6928. |
| PMID 11741938 |
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| Cyclooxygenase-2 and gastric carcinogenesis. |
| Saukkonen K, Rintahaka J, Sivula A, Buskens CJ, Van Rees BP, Rio MC, Haglund C, Van Lanschot JJ, Offerhaus GJ, Ristimaki A |
| APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2003 ; 111 (10) : 915-925. |
| PMID 14616542 |
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| Cyclooxygenase-2 inhibitors in lung cancer. |
| Ramalingam S, Belani CP |
| Clinical lung cancer. 2004 ; 5 (4) : 245-253. |
| PMID 14967078 |
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| Cyclooxygenases in cancer: progress and perspective. |
| Zha S, Yegnasubramanian V, Nelson WG, Isaacs WB, De Marzo AM |
| Cancer letters. 2004 ; 215 (1) : 1-20. |
| PMID 15374627 |
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| The cardiovascular toxicity of selective and nonselective cyclooxygenase inhibitors: comparisons, contrasts, and aspirin confounding. |
| Konstantinopoulos PA, Lehmann DF |
| Journal of clinical pharmacology. 2005 ; 45 (7) : 742-750. |
| PMID 15951464 |
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| COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies? |
| Raspollini MR, Susini T, Amunni G, Paglierani M, Taddei A, Marchionni M, Scarselli G, Taddei GL |
| Gynecologic oncology. 2005 ; 96 (1) : 159-167. |
| PMID 15589595 |
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| Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma. |
| Wu T |
| Biochimica et biophysica acta. 2005 ; 1755 (2) : 135-150. |
| PMID 15921858 |
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| Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression. |
| Rask K, Zhu Y, Wang W, Hedin L, Sundfeldt K |
| Molecular cancer. 2006 ; 5 : page 62. |
| PMID 17107625 |
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| NF-kappaB/PPAR gamma and/or AP-1/PPAR gamma 'on/off' switches and induction of CBP in colon adenocarcinomas: correlation with COX-2 expression. |
| Konstantinopoulos PA, Vandoros GP, Sotiropoulou-Bonikou G, Kominea A, Papavassiliou AG |
| International journal of colorectal disease. 2007 ; 22 (1) : 57-68. |
| PMID 16506021 |
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