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Gene Review

PTGS2  -  prostaglandin-endoperoxide synthase 2...

Homo sapiens

Synonyms: COX-2, COX2, Cyclooxygenase-2, GRIPGHS, PGG/HS, ...

Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase or COX , is a rate-limiting enzyme in the conversion of arachidonic acid, a product of damaged cell membranes, into prostaglandins. PTGS exist in at least 2 isoforms, PTGS1 (COX-1), and PTGS2 (COX-2). PTGS1 is constitutively expressed in many tissues and is the predominant form in gastric mucosa and in the kidneys. PTGS2 is unexpressed under normal conditions, but elevated levels are found during inflammation which is induced by cytokines and growth factors. Among other prostaglandins, PTGS2 activation produces prostaglandin E2 (PGE2), which acts on a number of cell signaling pathways involving cell proliferation, angiogenesis, apoptosis inhibition, invasion,immune response suppression, and tumor cell invasion and metastasis which could increase cancer progression. Hypoxia led to a preferential PTGS2 induction in tumor cells and fostered ahigher metastatic take of tumor cells [1].

There is strong evidence that PTGS2 expressed in most solid tumor types. Cellular expression of PTGS2 is increased in the earliest stages of carcinogenesis and through tumor development and invasive tumor growth.A large number of studies have examined  that PTGS2 up regulation is particularly common and associated with worse survival among colon cancer patients [2].PTGS2 genotype is also be found  associated with breast cancer,biliary tract cancer and colorectal cancer [3] [4][5].PTGS2 CpG island hypermethylation portended an increased risk of recurrence in human prostate cancer [6].In PTGS2 -positive pancreatic cancer, the nimesulide-induced increase of VEGF production by the cancer cells was offset by a decrease in VEGF production by the nonmalignant cell types leading to reduced tumor angiogenesis and growth[7].PTGS-2 overexpression is observed in breast cancer and has been associated with indicators of poor prognosis, such as lymph node metastasis, poor differentiation, and large tumor size. Furthermore, inhibition of PTGS-2 by nonsteroidal anti-inflammatory drugs has been associated with a protective effect against a variety of cancers and may be effective in the prevention and treatment of breast cancer.Evidence is emerging that the use of nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin or selective PTGS2 inhibitors celecoxib, may reduce risk of colorectal cancer.And it is almost consensus that  PTGS2 has been associated with the breast cancer and patient prognosis. However, not all breast cancer patients has the abnormal in PTGS2 gene or PTGS2 expression, so it is still indeterminacy that PTGS2 can be defined as diagnostic markers or drug target.


The Cancer Genome Atlas (TCGA) Data Portal provides a platform for cancer research which also including bound of breast cancer datas contains genomic characterization data, clinical information,and so on. Tumor and germline DNA samples were obtained from 825 patients.The Cancer Genome Atlas Network [8]


In this study, we systematically evaluated the biologically interesting features of PTGS2 alteration and the relationship with breast cancer prognosis from The Cancer Genome Atlas (TCGA). Finally, we related our results to distinct patterns of EMT activation in different subtypes and characterized their prognostic effects. Therefore, the expression of the genes in this study clearly revealed the evidence that elucidates their functional significance between the molecular environments. Our findings also have important implications for glioma biology and heterogeneity and possible therapeutic intervention for patients with GBM.The aim of the study was to systematically identify all studies that analyzed the association between PTGS2 expression in colorectal tumors at diagnosis and subsequent survival and/or recurrence and to clarify the associations using meta-analyses.


Associations of PTGS2 with chemical compounds

  • Thus the results indicate the need for further investigation toward PTGS2 pharmacogenetics-based prescription of celecoxib [9].
  • Although the mechanisms by which NSAIDs lower cancer risk remain unclear, NSAIDs reduce prostaglandin production by blocking prostaglandin-endoperoxide synthase 2 (PTGS2, commonly known as COX-2), an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue [3].
  • These findings indicate that genetic variants in PTGS2 may play a role in mediating susceptibility to T2DM in Pima Indians and are consistent with the hypothesis that chronic inflammation may contribute to the development of T2DM in some individuals [10].
  • CONCLUSION(S): Monkey OSE expresses mRNA for PTGS1, PTGS2, and all PGE synthases and produces PGE(2) both before and 36 hours after hCG [11].
  • Our data indicate that F-IPF have a striking defect in their capacity to synthesize the antiinflammatory and antifibrogenic molecule PGE2, apparently because of a diminished induction of COX-2 protein [12].
  • GS-HCl (5 mM) also facilitated degradation of the higher molecular species of COX-2 in IL-1beta-treated A549 cells that was retarded by MG132 [13].
  • Inhibition of Cn activity by the immunosuppressive drug cyclosporin A impaired NFAT activation and diminished Cox-2 expression in BBS-stimulated cells [14].

Physical interactions of PTGS2

  • Here we describe two heterodimers in which a native subunit of human PGHS-2 has been coupled to a subunit having a defect within the COX active site at some distance from the dimer interface [15].
  • Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein [16].
  • Recent evidence suggests that cyclooxygenase-2 (COX-2) modulates angiogenesis by interacting with the VEGF system [17].
  • Cyclooxygenase-2 interacts with p53 and interferes with p53-dependent transcription and apoptosis [18].
  • The ability of PPARgamma ligands to inhibit COX-2 appears to be mediated predominantly through inhibition of AP-1 protein binding to the CRE site in the COX-2 promoter [19].

Co-localisations of PTGS2


Regulatory relationships of PTGS2


Other interactions of PTGS2


Analytical, diagnostic and therapeutic context of PTGS2



Tumor size, histologic grade, presence of primarylymph node metastases, or age atdiagnosis were not associated with the genotypes [4].


  1. Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic hypoxia: effect on angiogenesis and metastases. Daneau, G., Boidot, R., Martinive, P., Feron, O. Clin. Cancer Res. (2010) [Pubmed]
  2. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Ogino, S., Kirkner, G.J., Nosho, K., Irahara, N., Kure, S., Shima, K., Hazra, A., Chan, A.T., Dehari, R., Giovannucci, E.L., Fuchs, C.S. Clin. Cancer Res. (2008) [Pubmed]
  3. Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China. Sakoda, L.C., Gao, Y.T., Chen, B.E., Chen, J., Rosenberg, P.S., Rashid, A., Deng, J., Shen, M.C., Wang, B.S., Han, T.Q., Zhang, B.H., Cohen-Webb, H., Yeager, M., Welch, R., Chanock, S., Fraumeni, J.F., Hsing, A.W. Carcinogenesis (2006) [Pubmed]
  4. The cyclooxygenase-2 (PTGS2) 8473T>C polymorphism is associated with breast cancer risk. Langsenlehner, U., Yazdani-Biuki, B., Eder, T., Renner, W., Wascher, T.C., Paulweber, B., Weitzer, W., Samonigg, H., Krippl, P. Clin. Cancer Res. (2006) [Pubmed]
  5. Polymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) and risk of colorectal cancer. Cox, D.G., Pontes, C., Guino, E., Navarro, M., Osorio, A., Canzian, F., Moreno, V. Br. J. Cancer (2004) [Pubmed]
  6. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Yegnasubramanian, S., Kowalski, J., Gonzalgo, M.L., Zahurak, M., Piantadosi, S., Walsh, P.C., Bova, G.S., De Marzo, A.M., Isaacs, W.B., Nelson, W.G. Cancer Res. (2004) [Pubmed]
  7. Growth stimulation of COX-2-negative pancreatic cancer by a selective COX-2 inhibitor. Eibl, G., Takata, Y., Boros, L.G., Liu, J., Okada, Y., Reber, H.A., Hines, O.J. Cancer Res. (2005) [Pubmed]
  8. Comprehensive molecular portraits of human breast tumours.  Nature. (2012) [Pubmed]
  9. The cyclooxygenase 2 genetic variant -765G>C does not modulate the effects of celecoxib on prostaglandin E(2) production. Skarke, C., Reus, M., Schmidt, R., Grundei, I., Schuss, P., Geisslinger, G., L??tsch, J. Clin. Pharmacol. Ther. (2006) [Pubmed]
  10. Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians. Konheim, Y.L., Wolford, J.K. Hum. Genet. (2003) [Pubmed]
  11. Prostaglandin-endoperoxide synthase (PTGS1 and PTGS2) expression and prostaglandin production by normal monkey ovarian surface epithelium. Cabrera, R.A., Dozier, B.L., Duffy, D.M. Fertil. Steril. (2006) [Pubmed]
  12. Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2. Wilborn, J., Crofford, L.J., Burdick, M.D., Kunkel, S.L., Strieter, R.M., Peters-Golden, M. J. Clin. Invest. (1995) [Pubmed]
  13. Glucosamine hydrochloride specifically inhibits COX-2 by preventing COX-2 N-glycosylation and by increasing COX-2 protein turnover in a proteasome-dependent manner. Jang, B.C., Sung, S.H., Park, J.G., Park, J.W., Bae, J.H., Shin, D.H., Park, G.Y., Han, S.B., Suh, S.I. J. Biol. Chem. (2007) [Pubmed]
  14. Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells. Corral, R.S., Iñiguez, M.A., Duque, J., López-Pérez, R., Fresno, M. Oncogene (2007) [Pubmed]
  15. Partnering between monomers of cyclooxygenase-2 homodimers. Yuan, C., Rieke, C.J., Rimon, G., Wingerd, B.A., Smith, W.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein. Chen, J.J., Huang, W.C., Chen, C.C. Mol. Biol. Cell (2005) [Pubmed]
  17. Vasoactive factors and diabetic retinopathy: vascular endothelial growth factor, cycoloxygenase-2 and nitric oxide. Wilkinson-Berka, J.L. Curr. Pharm. Des. (2004) [Pubmed]
  18. Cyclooxygenase-2 interacts with p53 and interferes with p53-dependent transcription and apoptosis. Corcoran, C.A., He, Q., Huang, Y., Sheikh, M.S. Oncogene (2005) [Pubmed]
  19. Control of COX-2 gene expression through peroxisome proliferator-activated receptor gamma in human cervical cancer cells. Han, S., Inoue, H., Flowers, L.C., Sidell, N. Clin. Cancer Res. (2003) [Pubmed]
  20. Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Baker, C.S., Hall, R.J., Evans, T.J., Pomerance, A., Maclouf, J., Creminon, C., Yacoub, M.H., Polak, J.M. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  21. Cyclooxygenase-2 inhibitor (SC-236) suppresses activator protein-1 through c-Jun NH2-terminal kinase. Wong, B.C., Jiang, X.H., Lin, M.C., Tu, S.P., Cui, J.T., Jiang, S.H., Wong, W.M., Yuen, M.F., Lam, S.K., Kung, H.F. Gastroenterology (2004) [Pubmed]
  22. Role of Asn-382 and Thr-383 in activation and inactivation of human prostaglandin H synthase cyclooxygenase catalysis. Bambai, B., Rogge, C.E., Stec, B., Kulmacz, R.J. J. Biol. Chem. (2004) [Pubmed]
  23. The adenomatous polyposis coli tumor suppressor gene regulates expression of cyclooxygenase-2 by a mechanism that involves retinoic acid. Eisinger, A.L., Nadauld, L.D., Shelton, D.N., Peterson, P.W., Phelps, R.A., Chidester, S., Stafforini, D.M., Prescott, S.M., Jones, D.A. J. Biol. Chem. (2006) [Pubmed]
  24. MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Lin, S.K., Kok, S.H., Yeh, F.T., Kuo, M.Y., Lin, C.C., Wang, C.C., Goldring, S.R., Hong, C.Y. Arthritis Rheum. (2004) [Pubmed]
  25. Progesterone Receptor Plays a Major Antiinflammatory Role in Human Myometrial Cells by Antagonism of Nuclear Factor-{kappa}B Activation of Cyclooxygenase 2 Expression. Hardy, D.B., Janowski, B.A., Corey, D.R., Mendelson, C.R. Mol. Endocrinol. (2006) [Pubmed]
  26. The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression. Lara-Pezzi, E., Gómez-Gaviro, M.V., Gálvez, B.G., Mira, E., Iñiguez, M.A., Fresno, M., Martínez-A, C., Arroyo, A.G., López-Cabrera, M. J. Clin. Invest. (2002) [Pubmed]
  27. P53-mediated induction of Cox-2 counteracts p53- or genotoxic stress-induced apoptosis. Han, J.A., Kim, J.I., Ongusaha, P.P., Hwang, D.H., Ballou, L.R., Mahale, A., Aaronson, S.A., Lee, S.W. EMBO J. (2002) [Pubmed]
  28. Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade. Lasa, M., Mahtani, K.R., Finch, A., Brewer, G., Saklatvala, J., Clark, A.R. Mol. Cell. Biol. (2000) [Pubmed]
  29. Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and -independent mechanisms. Subbaramaiah, K., Cole, P.A., Dannenberg, A.J. Cancer Res. (2002) [Pubmed]
  30. Increased expression of cyclooxygenase-2 in human pancreatic islets treated with high glucose or ligands of the advanced glycation endproduct-specific receptor (AGER), and in islets from diabetic mice. Shanmugam, N., Todorov, I.T., Nair, I., Omori, K., Reddy, M.A., Natarajan, R. Diabetologia (2006) [Pubmed]
  31. PTGS2 (COX-2) -765G > C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Ulrich, C.M., Whitton, J., Yu, J.H., Sibert, J., Sparks, R., Potter, J.D., Bigler, J. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  32. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. McKenzie, L.J., Pangas, S.A., Carson, S.A., Kovanci, E., Cisneros, P., Buster, J.E., Amato, P., Matzuk, M.M. Hum. Reprod. (2004) [Pubmed]
  33. Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Kosaka, T., Miyata, A., Ihara, H., Hara, S., Sugimoto, T., Takeda, O., Takahashi, E., Tanabe, T. Eur. J. Biochem. (1994) [Pubmed]
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