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Expression of Prostaglandin G/H Synthase-1 and -2 Protein in Human Colon Cancer

Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe Claire-Dorval, Quebec H9R 4P8, Canada [S. L. K., G. P. O., J. F. E., J. A. M.]; Department of Molecular Sciences, Pfizer Central Research, Sandwich, Kent CT13 9NJ, England [P. J. V.]; and Department of Pathology, McGill University, Montreal, Quebec H3A 2B4, Canada [S. J.]

Prostaglandin G/H synthase (PGHS), a key enzyme leading to the formation of prostaglandins, is the target of nonsteroidal antiinflammatory drugs. Two forms of the enzyme have been identified, PGHS-1 and PGHS-2. Epidemiological evidence has suggested that aspirin and other nonsteroidal antiinflammatory drugs may reduce the risk of colorectal cancer. We examined by immunoblot analyses the expression of human PGHS-1 and PGHS-2 protein in 25 matched colon cancer and nontumor tissues, 4 premalignant polyps, 5 control colon tissues from noncancer patients, and 3 matched normal and cancerous breast tissue samples. PGHS-1 was detected in all normal and tumor tissue. In contrast, PGHS-2 was not detected in 23 of 25 normal colon tissues but was detected in 19 of 25 colon tumors. PGHS-2 protein was not observed in four human premalignant polyp samples, control colon from noncancer patients, or matched normal or cancerous breast tissues. These results suggest that the beneficial effects of nonsteroidal antiinflammatory drugs in colon cancer may be mediated by inhibition of PGHS-2.

¹ To whom requests for reprints should be addressed.

Received 1/30/95. Accepted 4/19/95.

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				S. RODRIGUES, Q.-D. NGUYEN, S. FAIVRE, E. BRUYNEEL, L. THIM, B. WESTLEY, F. MAY, G. FLATAU, M. MAREEL, C. GESPACH, et al. Activation of cellular invasion by trefoil peptides and src is mediated by cyclooxygenase- and thromboxane A2 receptor-dependent signaling pathways FASEB J, July 1, 2001; 15(9): 1517 - 1528. [Abstract] [Full Text] [PDF]

				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]

				R. J Bing Myocardial ischemia and infarction: growth of ideas Cardiovasc Res, July 1, 2001; 51(1): 13 - 20. [Abstract] [Full Text] [PDF]

				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]

				T. Shono, P. J. Tofilon, J. M. Bruner, O. Owolabi, and F. F. Lang Cyclooxygenase-2 Expression in Human Gliomas: Prognostic Significance and Molecular Correlations Cancer Res., June 1, 2001; 61(11): 4375 - 4381. [Abstract] [Full Text] [PDF]

				W A Brown, S A Skinner, C Malcontenti-Wilson, D Vogiagis, and P E O'Brien Non-steroidal anti-inflammatory drugs with activity against either cyclooxygenase 1 or cyclooxygenase 2 inhibit colorectal cancer in a DMH rodent model by inducing apoptosis and inhibiting cell proliferation Gut, May 1, 2001; 48(5): 660 - 666. [Abstract] [Full Text] [PDF]

				J. Bigler, J. Whitton, J. W. Lampe, L. Fosdick, R. M. Bostick, and J. D. Potter CYP2C9 and UGT1A6 Genotypes Modulate the Protective Effect of Aspirin on Colon Adenoma Risk Cancer Res., May 1, 2001; 61(9): 3566 - 3569. [Abstract] [Full Text]

				C. V. Rao, C-Q. Wang, B. Simi, J. G. Rodriguez, I. Cooma, K. El-Bayoumy, and B. S. Reddy Chemoprevention of Colon Cancer by a Glutathione Conjugate of 1,4-Phenylenebis(methylene)selenocyanate, a Novel Organoselenium Compound with Low Toxicity Cancer Res., May 1, 2001; 61(9): 3647 - 3652. [Abstract] [Full Text]

				G. L. Wiesner, P. Platzer, S. Buxbaum, S. Lewis, M. MacMillen, J. Olechnowicz, J. Willis, A. Chakravarti, R. C. Elston, and S. D. Markowitz Testing for Colon Neoplasia Susceptibility Variants at the Human COX2 Locus J Natl Cancer Inst, April 18, 2001; 93(8): 635 - 639. [Abstract] [Full Text] [PDF]

				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]

				C. V. Rao, Y. Hirose, C. Indranie, and B. S. Reddy Modulation of Experimental Colon Tumorigenesis by Types and Amounts of Dietary Fatty Acids Cancer Res., March 1, 2001; 61(5): 1927 - 1933. [Abstract] [Full Text]

				J. Liu, M. Antaya, A. K. Goff, D. Boerboom, D. W. Silversides, J. G. Lussier, and J. Sirois Molecular Characterization of Bovine Prostaglandin G/H Synthase-2 and Regulation in Uterine Stromal Cells Biol Reprod, March 1, 2001; 64(3): 983 - 991. [Abstract] [Full Text]

				M. D. Boudreau, K. H. Sohn, S. H. Rhee, S. W. Lee, J. D. Hunt, and D. H. Hwang Suppression of Tumor Cell Growth Both in Nude Mice and in Culture by n-3 Polyunsaturated Fatty Acids: Mediation through Cyclooxygenase-independent Pathways Cancer Res., February 1, 2001; 61(4): 1386 - 1391. [Abstract] [Full Text]

				H. Shiotani, A. Denda, K. Yamamoto, W. Kitayama, T. Endoh, Y. Sasaki, M. Tsutsumi, M. Sugimura, and Y. Konishi Increased Expression of Cyclooxygenase-2 Protein in 4-Nitroquinoline-1-oxide-induced Rat Tongue Carcinomas and Chemopreventive Efficacy of a Specific Inhibitor, Nimesulide Cancer Res., February 1, 2001; 61(4): 1451 - 1456. [Abstract] [Full Text]

				M. Oshima, N. Murai, S. Kargman, M. Arguello, P. Luk, E. Kwong, M. M. Taketo, and J. F. Evans Chemoprevention of Intestinal Polyposis in the Apc{{Delta}}716 Mouse by Rofecoxib, a Specific Cyclooxygenase-2 Inhibitor Cancer Res., February 1, 2001; 61(4): 1733 - 1740. [Abstract] [Full Text]

				F. W. Wiese, P. A. Thompson, and F. F. Kadlubar Carcinogen substrate specificity of human COX-1 and COX-2 Carcinogenesis, January 1, 2001; 22(1): 5 - 10. [Abstract] [Full Text] [PDF]

				L. Adam, A. Mazumdar, T. Sharma, T. R. Jones, and R. Kumar A Three-Dimensional and Temporo-Spatial Model to Study Invasiveness of Cancer Cells by Heregulin and Prostaglandin E2 Cancer Res., January 1, 2001; 61(1): 81 - 87. [Abstract] [Full Text]

				S Chariyalertsak, V Sirikulchayanonta, D Mayer, A Kopp-Schneider, G Furstenberger, F Marks, and K Muller-Decker Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma Gut, January 1, 2001; 48(1): 80 - 86. [Abstract] [Full Text] [PDF]

				C. Denkert, M. Köbel, S. Berger, A. Siegert, A. Leclere, U. Trefzer, and S. Hauptmann Expression of Cyclooxygenase 2 in Human Malignant Melanoma Cancer Res., January 1, 2001; 61(1): 303 - 308. [Abstract] [Full Text]

				L M Jackson, K C Wu, Y R Mahida, D Jenkins, and C J Hawkey Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa Gut, December 1, 2000; 47(6): 762 - 770. [Abstract] [Full Text] [PDF]

				Y Kishimoto, N Takata, T Jinnai, T Morisawa, G Shiota, H Kawasaki, and J Hasegawa Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane Gut, December 1, 2000; 47(6): 812 - 819. [Abstract] [Full Text] [PDF]

				R. A. Gupta, J. Tan, W. F. Krause, M. W. Geraci, T. M. Willson, S. K. Dey, and R. N. DuBois Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer PNAS, November 21, 2000; 97(24): 13275 - 13280. [Abstract] [Full Text] [PDF]

				C. W. Houchen, W. F. Stenson, and S. M. Cohn Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury Am J Physiol Gastrointest Liver Physiol, November 1, 2000; 279(5): G858 - G865. [Abstract] [Full Text] [PDF]

				C. S. Williams, A. J. M. Watson, H. Sheng, R. Helou, J. Shao, and R. N. DuBois Celecoxib Prevents Tumor Growth in Vivo without Toxicity to Normal Gut: Lack of Correlation between in Vitro and in Vivo Models Cancer Res., November 1, 2000; 60(21): 6045 - 6051. [Abstract] [Full Text]

				W.-L. Yang and H. Frucht Cholinergic receptor up-regulates COX-2 expression and prostaglandin E2 production in colon cancer cells Carcinogenesis, October 1, 2000; 21(10): 1789 - 1793. [Abstract] [Full Text] [PDF]

				M HULL, M LANGMAN;, J DIMBERG, and P SODERKVIST Differential expression of cyclooxygenase 2 in human colorectal cancer Reply Gut, July 1, 2000; 47(1): 154 - 154. [Full Text] [PDF]

				E. M. Grossman, W. E. Longo, N. Panesar, J. E. Mazuski, and D. L. Kaminski The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells Carcinogenesis, July 1, 2000; 21(7): 1403 - 1409. [Abstract] [Full Text] [PDF]