© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 455-460, Copyright © 1998 by Oxford University Press
D Hwang, D Scollard, J Byrne and E Levine
BACKGROUND: Numerous studies have demonstrated that the levels of
prostaglandins are greater in various cancers, including breast cancer and
colon cancer, than in normal tissues. In particular, the inducible form of
cyclooxygenase (COX), the rate-limiting enzyme in prostaglandin
biosynthesis, is overexpressed in colon tumors. Epidemiologic studies have
demonstrated that the use of aspirin or other nonsteroidal anti-
inflammatory drugs (NSAIDs) can reduce the risk of colon cancer and, to a
lesser extent, the risk of breast cancer. NSAIDs are known to inhibit COX,
suggesting that the beneficial effect of NSAIDs in colon cancer may be
related to COX overexpression in this disease. This possibility led us to
ask whether COX is also overexpressed in breast cancers. METHODS: Surgical
specimens from 44 patients with breast cancer who had undergone lumpectomy
or mastectomy were analyzed by immunoblot analysis and immunohistochemical
analysis to determine the expression profile of the constitutively
expressed form of cyclooxygenase (COX-1) and the inducible form (COX-2);
the specimens from 14 patients included normal breast tissue. RESULTS:
Expression of COX-1 protein was substantially higher in 30 of 44 tumor
samples than in any of the 14 normal tissue specimens. Immunoblot analysis
revealed extremely high levels of COX-2 protein in two tumor samples.
Immunohistochemical staining of specimens that expressed COX-1 and/or COX-2
revealed that COX-1 was localized in stromal cells adjacent to the tumor
but not in tumor cells. In contrast, COX-2 was localized primarily in tumor
cells but also appeared in stromal cells. CONCLUSION: Our results suggest
that overexpression of COX may not be unique to colon cancer and may be a
feature common to other epithelial tumors.
ARTICLES
Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. hwangdh@mhs.pbrc.edu
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A. Ristimaki, A. Sivula, J. Lundin, M. Lundin, T. Salminen, C. Haglund, H. Joensuu, and J. Isola Prognostic Significance of Elevated Cyclooxygenase-2 Expression in Breast Cancer Cancer Res., February 1, 2002; 62(3): 632 - 635. [Abstract] [Full Text] [PDF]
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 F. TOSETTI, N. FERRARI, S. DE FLORA, and A. ALBINI Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents FASEB J, January 1, 2002; 16(1): 2 - 14. [Abstract] [Full Text] [PDF]
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K. J. Sales, A. A. Katz, B. Howard, R. P. Soeters, R. P. Millar, and H. N. Jabbour Cyclooxygenase-1 Is Up-Regulated in Cervical Carcinomas: Autocrine/Paracrine Regulation of Cyclooxygenase-2, Prostaglandin E Receptors, and Angiogenic Factors by Cyclooxygenase-1 Cancer Res., January 1, 2002; 62(2): 424 - 432. [Abstract] [Full Text] [PDF]
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S. Zha, W. R. Gage, J. Sauvageot, E. A. Saria, M. J. Putzi, C. M. Ewing, D. A. Faith, W. G. Nelson, A. M. De Marzo, and W. B. Isaacs Cyclooxygenase-2 Is Up-Regulated in Proliferative Inflammatory Atrophy of the Prostate, but not in Prostate Carcinoma Cancer Res., December 1, 2001; 61(24): 8617 - 8623. [Abstract] [Full Text] [PDF]
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T. Kawamori, N. Uchiya, S. Nakatsugi, K. Watanabe, S. Ohuchida, H. Yamamoto, T. Maruyama, K. Kondo, T. Sugimura, and K. Wakabayashi Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on breast cancer development Carcinogenesis, December 1, 2001; 22(12): 2001 - 2004. [Abstract] [Full Text] [PDF]
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D. HWANG Modulation of the expression of cyclooxygenase-2 by fatty acids mediated through Toll-like receptor 4-derived signaling pathways FASEB J, December 1, 2001; 15(14): 2556 - 2564. [Abstract] [Full Text] [PDF]
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R. J. Bing, M. Miyataka, K. A. Rich, N. Hanson, X. Wang, H. D. Slosser, and S.-R. Shi Nitric Oxide, Prostanoids, Cyclooxygenase, and Angiogenesis in Colon and Breast Cancer Clin. Cancer Res., November 1, 2001; 7(11): 3385 - 3392. [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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R. D. Blumenthal, C. Waskewich, D. M. Goldenberg, W. Lew, C. Flefleh, and J. Burton Chronotherapy and Chronotoxicity of the Cyclooxygenase-2 Inhibitor, Celecoxib, in Athymic Mice Bearing Human Breast Cancer Xenografts Clin. Cancer Res., October 1, 2001; 7(10): 3178 - 3185. [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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R. N. DuBois Cyclooxygenease-2 and Hepatocellular Carcinoma: Is It a Target for Prevention? Clin. Cancer Res., May 1, 2001; 7(5): 1110 - 1110. [Full Text]
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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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V. Subbarayan, A. L. Sabichi, N. Llansa, S. M. Lippman, and D. G. Menter Differential Expression of Cyclooxygenase-2 and Its Regulation by Tumor Necrosis Factor-{{alpha}} in Normal and Malignant Prostate Cells Cancer Res., March 1, 2001; 61(6): 2720 - 2726. [Abstract] [Full Text]
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C. J. Grubbs, R. A. Lubet, A. T. Koki, K. M. Leahy, J. L. Masferrer, V. E. Steele, G. J. Kelloff, D. L. Hill, and K. Seibert Celecoxib Inhibits N-Butyl-N-(4-hydroxybutyl)-nitrosamine-induced Urinary Bladder Cancers in Male B6D2F1 Mice and Female Fischer-344 Rats Cancer Res., October 1, 2000; 60(20): 5599 - 5602. [Abstract] [Full Text]
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N. Rioux and A. Castonguay The induction of cyclooxygenase-1 by a tobacco carcinogen in U937 human macrophages is correlated to the activation of NF-{kappa}B Carcinogenesis, September 1, 2000; 21(9): 1745 - 1751. [Abstract] [Full Text] [PDF]
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J. A. Williams and D. H. Phillips Mammary Expression of Xenobiotic Metabolizing Enzymes and Their Potential Role in Breast Cancer Cancer Res., September 1, 2000; 60(17): 4667 - 4677. [Abstract] [Full Text]
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S. A. Wardlaw, T. H. March, and S. A. Belinsky Cyclooxygenase-2 expression is abundant in alveolar type II cells in lung cancer-sensitive mouse strains and in premalignant lesions Carcinogenesis, July 1, 2000; 21(7): 1371 - 1377. [Abstract] [Full Text] [PDF]
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M. Komhoff, Y. Guan, H. W. Shappell, L. Davis, G. Jack, Y. Shyr, M. O. Koch, S. B. Shappell, and M. D. Breyer Enhanced Expression of Cyclooxygenase-2 in High Grade Human Transitional Cell Bladder Carcinomas Am. J. Pathol., July 1, 2000; 157(1): 29 - 35. [Abstract] [Full Text] [PDF]
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A.-L. Hsu, T.-T. Ching, D.-S. Wang, X. Song, V. M. Rangnekar, and C.-S. Chen The Cyclooxygenase-2 Inhibitor Celecoxib Induces Apoptosis by Blocking Akt Activation in Human Prostate Cancer Cells Independently of Bcl-2 J. Biol. Chem., April 6, 2000; 275(15): 11397 - 11403. [Abstract] [Full Text] [PDF]
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A. K. Bauer, L. D. Dwyer-Nield, and A. M. Malkinson High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors Carcinogenesis, April 1, 2000; 21(4): 543 - 550. [Abstract] [Full Text] [PDF]
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A. Shamma, H. Yamamoto, Y. Doki, J. Okami, M. Kondo, Y. Fujiwara, M. Yano, M. Inoue, N. Matsuura, H. Shiozaki, et al. Up-Regulation of Cyclooxygenase-2 in Squamous Carcinogenesis of the Esophagus Clin. Cancer Res., April 1, 2000; 6(4): 1229 - 1238. [Abstract] [Full Text]
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K. Uefuji, T. Ichikura, and H. Mochizuki Cyclooxygenase-2 Expression Is Related to Prostaglandin Biosynthesis and Angiogenesis in Human Gastric Cancer Clin. Cancer Res., January 1, 2000; 6(1): 135 - 138. [Abstract] [Full Text]
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A. J. Trimboli, B. M. Waite, G.-i. Atsumi, A. N. Fonteh, A. M. Namen, C. E. Clay, T. E. Kute, K. P. High, M. C. Willingham, and F. H. Chilton Influence of Coenzyme A-independent Transacylase and Cyclooxygenase Inhibitors on the Proliferation of Breast Cancer Cells Cancer Res., December 1, 1999; 59(24): 6171 - 6177. [Abstract] [Full Text] [PDF]
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M. Kondo, H. Yamamoto, H. Nagano, J. Okami, Y. Ito, J. Shimizu, H. Eguchi, A. Miyamoto, K. Dono, K. Umeshita, et al. Increased Expression of COX-2 in Nontumor Liver Tissue Is Associated with Shorter Disease-free Survival in Patients with Hepatocellular Carcinoma Clin. Cancer Res., December 1, 1999; 5(12): 4005 - 4012. [Abstract] [Full Text] [PDF]
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S. I. Mohammed, D. W. Knapp, D. G. Bostwick, R. S. Foster, K. N. M. Khan, J. L. Masferrer, B. M. Woerner, P. W. Snyder, and A. T. Koki Expression of Cyclooxygenase-2 (COX-2) in Human Invasive Transitional Cell Carcinoma (TCC) of the Urinary Bladder Cancer Res., November 1, 1999; 59(22): 5647 - 5650. [Abstract] [Full Text] [PDF]
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C. Tremblay, M. Dore, P. N. Bochsler, and J. Sirois Induction of Prostaglandin G/H Synthase-2 in a Canine Model of Spontaneous Prostatic Adenocarcinoma J Natl Cancer Inst, August 18, 1999; 91(16): 1398 - 1403. [Abstract] [Full Text] [PDF]
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