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Departments of Clinical Chemistry [A. R., N. H., H. J., M. H.] and Obstetrics and Gynecology [A. R.], the Haartman Institute [A. R.], University of Helsinki, Haartmaninkatu 2, SF-00290 Helsinki, Finland, and Jorvi Hospital, Espoo, Finland [P. S.]
Epidemiological studies suggest that the use of aspirin decreases the incidence of and mortality from gastrointestinal cancers. The best known target of aspirin and other nonsteroidal anti-inflammatory drugs is cy-clooxygenase (Cox), the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned, of which Cox-2 is an inducible immediate-early gene. It is still unknown how nonsteroidal anti-inflammatory drugs act as chemopreventive agents, but they may target Cox-2. Cox-2 mRNA and protein were recently found to be expressed in human colon carcinoma. We have now studied the expression of Cox-2 in human gastric adenocarcinoma tissues which contained significantly higher levels of Cox-2 mRNA when compared with paired gastric mucosal specimens devoid of cancer cells. In contrast, Cox-1 mRNA levels were not elevated in the carcinoma. However, Cox-2 mRNA was not expressed in mucinous ovarian carcinoma samples as detected by Northern blot hybridization. Immunohistological detection of Cox-2 protein showed cytoplasmic staining in the gastric carcinoma cells but not in the surrounding stroma. Some hyperplastic glands showed intense staining, whereas glands of normal morphology were negative. Our data thus suggest that Cox-2 is expressed by human gastric adenocarcinoma.
1 Supported by the Academy of Finland and Helsinki University Central Hospital Research Funds.
2 To whom requests for reprints should be addressed, at Research Laboratory, Department of Obstetrics and Gynecology, Haartman Institute, University of Helsinki, Haartmaninkatu 2, SF-00290 Helsinki, Finland. Phone: 358-9-471-4981; Fax: 358-9-471-4801.
Received 11/ 5/96. Accepted 2/ 8/97.
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G. Liu, W.-Y. Ma, A. M. Bode, Y. Zhang, and Z. Dong NS-398 and Piroxicam Suppress UVB-induced Activator Protein 1 Activity by Mechanisms Independent of Cyclooxygenase-2 J. Biol. Chem., January 17, 2003; 278(4): 2124 - 2130. [Abstract] [Full Text] [PDF]
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Y. Sun, X. M. Tang, E. Half, M. T. Kuo, and F. A. Sinicrope Cyclooxygenase-2 Overexpression Reduces Apoptotic Susceptibility by Inhibiting the Cytochrome c-dependent Apoptotic Pathway in Human Colon Cancer Cells Cancer Res., November 1, 2002; 62(21): 6323 - 6328. [Abstract] [Full Text] [PDF]
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 M. L. Nasi and M. Castiglione Cyclooxygenase-2 (COX-2) a new prognostic and predictive factor for ovarian cancer? Are all the criteria fulfilled? Ann. Onc., August 1, 2002; 13(8): 1169 - 1171. [Full Text] [PDF]
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P. S. Carlton, R. Gopalakrishnan, A. Gupta, B. W. Liston, S. Habib, M. A. Morse, and G. D. Stoner Piroxicam Is an Ineffective Inhibitor of N-Nitrosomethylbenzylamine-induced Tumorigenesis in the Rat Esophagus Cancer Res., August 1, 2002; 62(15): 4376 - 4382. [Abstract] [Full Text] [PDF]
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B. S. Kaur and G. Triadafilopoulos Acid- and bile-induced PGE2 release and hyperproliferation in Barrett's esophagus are COX-2 and PKC-epsilon dependent Am J Physiol Gastrointest Liver Physiol, August 1, 2002; 283(2): G327 - G334. [Abstract] [Full Text] [PDF]
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M. Tamura, S. Sebastian, S. Yang, B. Gurates, K. Ferrer, H. Sasano, K. Okamura, and S. E. Bulun Up-regulation of Cyclooxygenase-2 Expression and Prostaglandin Synthesis in Endometrial Stromal Cells by Malignant Endometrial Epithelial Cells. A PARACRINE EFFECT MEDIATED BY PROSTAGLANDIN E2 AND NUCLEAR FACTOR-kappa B J. Biol. Chem., July 12, 2002; 277(29): 26208 - 26216. [Abstract] [Full Text] [PDF]
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 S. Lajoie, J. Sirois, and M. Dore Induction of Cyclo-oxygenase-2 Expression in Naturally Occurring Gastric Ulcers J. Histochem. Cytochem., July 1, 2002; 50(7): 923 - 934. [Abstract] [Full Text] [PDF]
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N. Pausawasdi, S. Ramamoorthy, L. J. Crofford, F. K. Askari, and A. Todisco Regulation and function of COX-2 gene expression in isolated gastric parietal cells Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G1069 - G1078. [Abstract] [Full Text] [PDF]
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K. Subbaramaiah, L. Norton, W. Gerald, and A. J. Dannenberg Cyclooxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer. EVIDENCE FOR INVOLVEMENT OF AP-1 AND PEA3 J. Biol. Chem., May 17, 2002; 277(21): 18649 - 18657. [Abstract] [Full Text] [PDF]
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 A. R. Munkarah, R. Morris, P. Baumann, G. Deppe, J. Malone, M. P. Diamond, and G. M. Saed Effects of Prostaglandin E2 on Proliferation and Apoptosis of Epithelial Ovarian Cancer Cells Reproductive Sciences, May 1, 2002; 9(3): 168 - 173. [Abstract] [PDF]
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K. Subbaramaiah, P. A. Cole, and A. J. Dannenberg Retinoids and Carnosol Suppress Cyclooxygenase-2 Transcription by CREB-binding Protein/p300-dependent and -independent Mechanisms Cancer Res., May 1, 2002; 62(9): 2522 - 2530. [Abstract] [Full Text] [PDF]
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T. Asano, J. Shoda, T. Ueda, T. Kawamoto, T. Todoroki, M. Shimonishi, T. Tanabe, Y. Sugimoto, A. Ichikawa, M. Mutoh, et al. Expressions of Cyclooxygenase-2 and Prostaglandin E-Receptors in Carcinoma of the Gallbladder: Crucial Role of Arachidonate Metabolism in Tumor Growth and Progression Clin. Cancer Res., April 1, 2002; 8(4): 1157 - 1167. [Abstract] [Full Text] [PDF]
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E. Half, X. M. Tang, K. Gwyn, A. Sahin, K. Wathen, and F. A. Sinicrope Cyclooxygenase-2 Expression in Human Breast Cancers and Adjacent Ductal Carcinoma in Situ Cancer Res., March 1, 2002; 62(6): 1676 - 1681. [Abstract] [Full Text] [PDF]
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 C. Denkert, M. Kobel, S. Pest, I. Koch, S. Berger, M. Schwabe, A. Siegert, A. Reles, B. Klosterhalfen, and S. Hauptmann Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma Am. J. Pathol., March 1, 2002; 160(3): 893 - 903. [Abstract] [Full Text] [PDF]
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T. Niki, T. Kohno, S. Iba, Y. Moriya, Y. Takahashi, M. Saito, A. Maeshima, T. Yamada, Y. Matsuno, M. Fukayama, et al. Frequent Co-Localization of Cox-2 and Laminin-5 {gamma}2 Chain at the Invasive Front of Early-Stage Lung Adenocarcinomas Am. J. Pathol., March 1, 2002; 160(3): 1129 - 1141. [Abstract] [Full Text] [PDF]
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M. J. Thun, S. J. Henley, and C. Patrono Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues J Natl Cancer Inst, February 20, 2002; 94(4): 252 - 266. [Abstract] [Full Text] [PDF]
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 M. C. Specht, O. N. Tucker, M. Hocever, D. Gonzalez, L. Teng, and T. J. Fahey III Cyclooxygenase-2 Expression in Thyroid Nodules J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 358 - 363. [Abstract] [Full Text] [PDF]
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H Kainulainen, I Rantala, P Collin, T Ruuska, H Paivarinne, T Halttunen, K Lindfors, K Kaukinen, and M Maki Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2 Gut, January 1, 2002; 50(1): 84 - 89. [Abstract] [Full Text] [PDF]
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G. B. Mills Mechanisms Underlying Chemoprevention of Ovarian Cancer Clin. Cancer Res., January 1, 2002; 8(1): 7 - 10. [Abstract] [Full Text] [PDF]
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Y. Cao, K. B. Dave, T. P. Doan, and S. M. Prescott Fatty Acid CoA Ligase 4 Is Up-Regulated in Colon Adenocarcinoma Cancer Res., December 1, 2001; 61(23): 8429 - 8434. [Abstract] [Full Text] [PDF]
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K. Yoshimatsu, D. Golijanin, P. B. Paty, R. A. Soslow, P.-J. Jakobsson, R. A. DeLellis, K. Subbaramaiah, and A. J. Dannenberg Inducible Microsomal Prostaglandin E Synthase Is Overexpressed in Colorectal Adenomas and Cancer Clin. Cancer Res., December 1, 2001; 7(12): 3971 - 3976. [Abstract] [Full Text] [PDF]
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W. Thomas, Z. K. Ascott, D. Harmey, L. W. Slice, E. Rozengurt, and A. J. Lax Cytotoxic Necrotizing Factor from Escherichia coli Induces RhoA-Dependent Expression of the Cyclooxygenase-2 Gene Infect. Immun., November 1, 2001; 69(11): 6839 - 6845. [Abstract] [Full Text] [PDF]
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 E. Fritsche, S. J. Baek, L. M. King, D. C. Zeldin, T. E. Eling, and D. A. Bell Functional Characterization of Cyclooxygenase-2 Polymorphisms J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 468 - 476. [Abstract] [Full Text] [PDF]
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K. Salmenkivi, C. Haglund, A. Ristimaki, J. Arola, and P. Heikkila Increased Expression of Cyclooxygenase-2 in Malignant Pheochromocytomas J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5615 - 5619. [Abstract] [Full Text] [PDF]
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J. Fujita, J. R. Mestre, J. B. Zeldis, K. Subbaramaiah, and A. J. Dannenberg Thalidomide and Its Analogues Inhibit Lipopolysaccharide-mediated Induction of Cyclooxygenase-2 Clin. Cancer Res., November 1, 2001; 7(11): 3349 - 3355. [Abstract] [Full Text] [PDF]
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A. H. Klimp, H. Hollema, C. Kempinga, A. G. J. van der Zee, E. G. E. de Vries, and T. Daemen Expression of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in Human Ovarian Tumors and Tumor-associated Macrophages Cancer Res., October 1, 2001; 61(19): 7305 - 7309. [Abstract] [Full Text] [PDF]
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 J.R. Paterson and J.R. Lawrence Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer QJM, August 1, 2001; 94(8): 445 - 448. [Abstract] [Full Text] [PDF]
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E. M. P. de Almeida, C. Piche, J. Sirois, and M. Dore Expression of Cyclo-oxygenase-2 in Naturally Occurring Squamous Cell Carcinomas in Dogs J. Histochem. Cytochem., July 1, 2001; 49(7): 867 - 876. [Abstract] [Full Text] [PDF]
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K. Saukkonen, O. Nieminen, B. van Rees, S. Vilkki, M. Harkonen, M. Juhola, J.-P. Mecklin, P. Sipponen, and A. Ristimaki Expression of Cyclooxygenase-2 in Dysplasia of the Stomach and in Intestinal-type Gastric Adenocarcinoma Clin. Cancer Res., July 1, 2001; 7(7): 1923 - 1931. [Abstract] [Full Text] [PDF]
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D. Vogiagis, W. Brown, E. M. Glare, and P. E. O'Brien Rat colorectal tumours treated with a range of non-steroidal anti-inflammatory drugs show altered cyclooxygenase-2 and cyclooxygenase-1 splice variant mRNA expression levels Carcinogenesis, June 1, 2001; 22(6): 869 - 874. [Abstract] [Full Text] [PDF]
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S. Hyun Song, H.-S. Jong, H. H. Choi, H. Inoue, T. Tanabe, N. K. Kim, and Y.-J. Bang Transcriptional Silencing of Cyclooxygenase-2 by Hyper-methylation of the 5' CpG Island in Human Gastric Carcinoma Cells Cancer Res., June 1, 2001; 61(11): 4628 - 4635. [Abstract] [Full Text] [PDF]
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S. Murono, H. Inoue, T. Tanabe, I. Joab, T. Yoshizaki, M. Furukawa, and J. S. Pagano Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells PNAS, May 24, 2001; (2001) 121016998. [Abstract] [Full Text] [PDF]
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 K. Subbaramaiah, P. Bulic, Y. Lin, A. J. Dannenberg, and D. S. Pasco Development and Use of a Gene Promoter-Based Screen to Identify Novel Inhibitors of Cyclooxygenase-2 Transcription J Biomol Screen, April 1, 2001; 6(2): 101 - 110. [Abstract] [PDF]
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Z. Li, Y. Shimada, A. Kawabe, F. Sato, M. Maeda, I. Komoto, T. Hong, Y. Ding, J. Kaganoi, and M. Imamura Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by JTE-522, a selective COX-2 inhibitor Carcinogenesis, April 1, 2001; 22(4): 547 - 551. [Abstract] [Full Text] [PDF]
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F. Biramijamal, A. Allameh, P. Mirbod, H.-J. Groene, R. Koomagi, and M. Hollstein Unusual Profile and High Prevalence of p53 Mutations in Esophageal Squamous Cell Carcinomas from Northern Iran Cancer Res., April 1, 2001; 61(7): 3119 - 3123. [Abstract] [Full Text]
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M. Akhtar, Y. Cheng, R. M. Magno, H. Ashktorab, D. T. Smoot, S. J. Meltzer, and K. T. Wilson Promoter Methylation Regulates Helicobacter pylori-stimulated Cyclooxygenase-2 Expression in Gastric Epithelial Cells Cancer Res., March 1, 2001; 61(6): 2399 - 2403. [Abstract] [Full Text]
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A. Ristimaki, O. Nieminen, K. Saukkonen, K. Hotakainen, S. Nordling, and C. Haglund Expression of Cyclooxygenase-2 in Human Transitional Cell Carcinoma of the Urinary Bladder Am. J. Pathol., March 1, 2001; 158(3): 849 - 853. [Abstract] [Full Text] [PDF]
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