This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zha, S. Articles by Isaacs, W. B. Search for Related Content PubMed PubMed Citation Articles by Zha, S. Articles by Isaacs, W. B.

Cyclooxygenase-2 Is Up-Regulated in Proliferative Inflammatory Atrophy of the Prostate, but not in Prostate Carcinoma¹

Graduate Program of Pharmacology and Molecular Sciences [S. Z], Brady Urological Institute [J. S., C. M. E., D. A. F., W. G. N., W. B. I.], and Department of Pathology [W. R. G., E. A. S., M. J. P., A. M. D.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Cyclooxygenase-2 (COX-2) is the inducible isoform of the rate-limiting enzymes that convert arachidonic acid to proinflammatory prostaglandins as well as a primary target for nonsteroidal anti-inflammatory drugs. Accumulating evidence suggests that up-regulation of COX-2 is associated with carcinogenesis in multiple organ systems including the large bowel, lung, breast, and prostate. In this report, we examine the expression of COX-2 protein and mRNA in prostate tissue containing various lesions and in prostate cancer cell lines. In the cell lines, LNCaP, DU145, PC-3, and TSU, COX-2 protein expression was undetectable under basal conditions but could be induced transiently by phorbol ester treatment in PC-3 and TSU cells, but not in DU145 and LNCaP cells. Immunohistochemical analysis of 144 human prostate cancer cases suggested that, in contrast to several previous reports, there was no consistent overexpression of COX-2 in established prostate cancer or high-grade prostatic intraepithelial neoplasia, as compared with adjacent normal prostate tissue. Positive staining was seen only in scattered cells (<1%) in both tumor and normal tissue regions but was much more consistently observed in areas of proliferative inflammatory atrophy, lesions that have been implicated in prostatic carcinogenesis. Staining was also seen at times in macrophages. Western blotting and quantitative RT-PCR analyses confirmed these patterns of expression. These results suggest that if nonsteroidal anti-inflammatory drugs are indeed chemopreventive and/or chemotherapeutic for prostate cancer, their effects are likely to be mediated by modulating COX-2 activity in non-PCa cells (either inflammatory cells or atrophic epithelial cells) or by affecting a COX-2-independent pathway.

This article has been cited by other articles:

				P. Fernandez, P. M. de Beer, L. van der Merwe, and C. F. Heyns COX-2 promoter polymorphisms and the association with prostate cancer risk in South African men Carcinogenesis, December 1, 2008; 29(12): 2347 - 2350. [Abstract] [Full Text] [PDF]

				A. Mehar, P. Macanas-Pirard, A. Mizokami, Y. Takahashi, G. E. N. Kass, and H. M. Coley The Effects of Cyclooxygenase-2 Expression in Prostate Cancer Cells: Modulation of Response to Cytotoxic Agents J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1181 - 1187. [Abstract] [Full Text] [PDF]

				X. Wang, J. K.L. Colby, P. Yang, S. M. Fischer, R. A. Newman, and R. D. Klein The resistance to the tumor suppressive effects of COX inhibitors and COX-2 gene disruption in TRAMP mice is associated with the loss of COX expression in prostate tissue Carcinogenesis, January 1, 2008; 29(1): 120 - 128. [Abstract] [Full Text] [PDF]

				N. N.C. Tam, I. Leav, and S.-M. Ho Sex Hormones Induce Direct Epithelial and Inflammation-Mediated Oxidative/Nitrosative Stress That Favors Prostatic Carcinogenesis in the Noble Rat Am. J. Pathol., October 1, 2007; 171(4): 1334 - 1341. [Abstract] [Full Text] [PDF]

				E. J. Quann, F. Khwaja, K. H. Zavitz, and D. Djakiew The Aryl Propionic Acid R-Flurbiprofen Selectively Induces p75NTR-Dependent Decreased Survival of Prostate Tumor Cells Cancer Res., April 1, 2007; 67(7): 3254 - 3262. [Abstract] [Full Text] [PDF]

				S. Swami, A. V. Krishnan, J. Moreno, R. B. Bhattacharyya, D. M. Peehl, and D. Feldman Calcitriol and Genistein Actions to Inhibit the Prostaglandin Pathway: Potential Combination Therapy to Treat Prostate Cancer J. Nutr., January 1, 2007; 137(1): 205S - 210S. [Abstract] [Full Text] [PDF]

				C. R. Bethel, D. Faith, X. Li, B. Guan, J. L. Hicks, F. Lan, R. B. Jenkins, C. J. Bieberich, and A. M. De Marzo Decreased NKX3.1 Protein Expression in Focal Prostatic Atrophy, Prostatic Intraepithelial Neoplasia, and Adenocarcinoma: Association with Gleason Score and Chromosome 8p Deletion. Cancer Res., November 15, 2006; 66(22): 10683 - 10690. [Abstract] [Full Text] [PDF]

				B. Knudsen Migrating with Myosin VI Am. J. Pathol., November 1, 2006; 169(5): 1523 - 1526. [Full Text] [PDF]

				R. N. DuBois Cyclooxygenase-2 Selective Inhibitors and Prostate Cancer: What Is the Clinical Benefit? J. Clin. Oncol., June 20, 2006; 24(18): 2691 - 2693. [Full Text] [PDF]

				M. R. Smith, J. Manola, D. S. Kaufman, W. K. Oh, G. J. Bubley, and P. W. Kantoff Celecoxib Versus Placebo for Men With Prostate Cancer and a Rising Serum Prostate-Specific Antigen After Radical Prostatectomy and/or Radiation Therapy J. Clin. Oncol., June 20, 2006; 24(18): 2723 - 2728. [Abstract] [Full Text] [PDF]

				C Hughes, A Murphy, C Martin, O Sheils, and J O'Leary Molecular pathology of prostate cancer J. Clin. Pathol., July 1, 2005; 58(7): 673 - 684. [Abstract] [Full Text] [PDF]

				G. S. Palapattu, S. Sutcliffe, P. J. Bastian, E. A. Platz, A. M. De Marzo, W. B. Isaacs, and W. G. Nelson Prostate carcinogenesis and inflammation: emerging insights Carcinogenesis, July 1, 2005; 26(7): 1170 - 1181. [Abstract] [Full Text] [PDF]

				P. J. Bastian, J. Ellinger, A. Wellmann, N. Wernert, L. C. Heukamp, S. C. Muller, and A. von Ruecker Diagnostic and Prognostic Information in Prostate Cancer with the Help of a Small Set of Hypermethylated Gene Loci Clin. Cancer Res., June 1, 2005; 11(11): 4097 - 4106. [Abstract] [Full Text] [PDF]

				J. N. Davis, M. T. McCabe, S. W. Hayward, J. M. Park, and M. L. Day Disruption of Rb/E2F Pathway Results in Increased Cyclooxygenase-2 Expression and Activity in Prostate Epithelial Cells Cancer Res., May 1, 2005; 65(9): 3633 - 3642. [Abstract] [Full Text] [PDF]

				W. Wang, A. Bergh, and J.-E. Damber Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3250 - 3256. [Abstract] [Full Text] [PDF]

				M. I. Patel, K. Subbaramaiah, B. Du, M. Chang, P. Yang, R. A. Newman, C. Cordon-Cardo, H. T. Thaler, and A. J. Dannenberg Celecoxib Inhibits Prostate Cancer Growth: Evidence of a Cyclooxygenase-2-Independent Mechanism Clin. Cancer Res., March 1, 2005; 11(5): 1999 - 2007. [Abstract] [Full Text] [PDF]

				E. A. Platz, S. Rohrmann, J. D. Pearson, M. M. Corrada, D. J. Watson, A. M. De Marzo, P. K. Landis, E. J. Metter, and H. B. Carter Nonsteroidal Anti-inflammatory Drugs and Risk of Prostate Cancer in the Baltimore Longitudinal Study of Aging Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 390 - 396. [Abstract] [Full Text] [PDF]

				S. Zha and W. B. Isaacs A Nonclassic CCAAT Enhancer Element Binding Protein Binding Site Contributes to {alpha}-Methylacyl-CoA Racemase Expression in Prostate Cancer Mol. Cancer Res., February 1, 2005; 3(2): 110 - 118. [Abstract] [Full Text] [PDF]

				M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]

				D. S. Dandekar and B. L. Lokeshwar Inhibition of Cyclooxygenase (COX)-2 Expression by Tet-Inducible COX-2 Antisense cDNA in Hormone-Refractory Prostate Cancer Significantly Slows Tumor Growth and Improves Efficacy of Chemotherapeutic Drugs Clin. Cancer Res., December 1, 2004; 10(23): 8037 - 8047. [Abstract] [Full Text] [PDF]

				W. G. Nelson Prostate Cancer Prevention J. Nutr., November 1, 2004; 134(11): 3211S - 3212S. [Full Text] [PDF]

				J. A. Green, R. A. Stockton, C. Johnson, and B. S. Jacobson 5-Lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers Am J Physiol Cell Physiol, August 1, 2004; 287(2): C373 - C383. [Abstract] [Full Text] [PDF]

				S. Gupta, V. M. Adhami, M. Subbarayan, G. T. MacLennan, J. S. Lewin, U. O. Hafeli, P. Fu, and H. Mukhtar Suppression of Prostate Carcinogenesis by Dietary Supplementation of Celecoxib in Transgenic Adenocarcinoma of the Mouse Prostate Model Cancer Res., May 1, 2004; 64(9): 3334 - 3343. [Abstract] [Full Text] [PDF]

				S. Yegnasubramanian, J. Kowalski, M. L. Gonzalgo, M. Zahurak, S. Piantadosi, P. C. Walsh, G. S. Bova, A. M. De Marzo, W. B. Isaacs, and W. G. Nelson Hypermethylation of CpG Islands in Primary and Metastatic Human Prostate Cancer Cancer Res., March 15, 2004; 64(6): 1975 - 1986. [Abstract] [Full Text] [PDF]

				S. K. Kulp, Y.-T. Yang, C.-C. Hung, K.-F. Chen, J.-P. Lai, P.-H. Tseng, J. W. Fowble, P. J. Ward, and C.-S. Chen 3-Phosphoinositide-Dependent Protein Kinase-1/Akt Signaling Represents a Major Cyclooxygenase-2-Independent Target for Celecoxib in Prostate Cancer Cells Cancer Res., February 15, 2004; 64(4): 1444 - 1451. [Abstract] [Full Text] [PDF]

				Inflammation, Dietary Carcinogens, Glutathione S-Transferase {pi}, and Prostatic Carcinogenesis: WILLIAM G. NELSON, ANGELO M. DE MARZO, THEODORE L. DEWEESE, AND WILLIAM B. ISAACS, The Departments of Oncology, Urology, Pathology, Pharmacology, and Medicine, The Johns Hopkins University School of Medicine, and The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Toxicol Pathol, January 1, 2004; 32(1): 143 - 144. [PDF]

				S. Zha, S. Ferdinandusse, S. Denis, R. J. Wanders, C. M. Ewing, J. Luo, A. M. De Marzo, and W. B. Isaacs {alpha}-Methylacyl-CoA Racemase as an Androgen-Independent Growth Modifier in Prostate Cancer Cancer Res., November 1, 2003; 63(21): 7365 - 7376. [Abstract] [Full Text] [PDF]

				H. Choy and L. Milas Enhancing Radiotherapy With Cyclooxygenase-2 Enzyme Inhibitors: A Rational Advance? J Natl Cancer Inst, October 1, 2003; 95(19): 1440 - 1452. [Abstract] [Full Text] [PDF]

				M. Nakayama, C. J. Bennett, J. L. Hicks, J. I. Epstein, E. A. Platz, W. G. Nelson, and A. M. De Marzo Hypermethylation of the Human Glutathione S-Transferase-{pi} Gene (GSTP1) CpG Island Is Present in a Subset of Proliferative Inflammatory Atrophy Lesions but Not in Normal or Hyperplastic Epithelium of the Prostate: A Detailed Study Using Laser-Capture Microdissection Am. J. Pathol., September 1, 2003; 163(3): 923 - 933. [Abstract] [Full Text] [PDF]

				B. A. Narayanan, M. S. Condon, M. C. Bosland, N. K. Narayanan, and B. S. Reddy Suppression of N-Methyl-N-nitrosourea/Testosterone-induced Rat Prostate Cancer Growth by Celecoxib: Effects on Cyclooxygenase-2, Cell Cycle Regulation, and Apoptosis Mechanism(s) Clin. Cancer Res., August 1, 2003; 9(9): 3503 - 3513. [Abstract] [Full Text] [PDF]

				W. G. Nelson, A. M. De Marzo, and W. B. Isaacs Prostate Cancer N. Engl. J. Med., July 24, 2003; 349(4): 366 - 381. [Full Text] [PDF]

				S. B. Shappell, S. J. Olson, S. E. Hannah, S. Manning, R. L. Roberts, N. Masumori, M. Jisaka, W. E. Boeglin, V. Vader, D. S. Dave, et al. Elevated Expression of 12/15-Lipoxygenase and Cyclooxygenase-2 in a Transgenic Mouse Model of Prostate Carcinoma Cancer Res., May 1, 2003; 63(9): 2256 - 2267. [Abstract] [Full Text] [PDF]

				G. J. L. H. van Leenders, W. R. Gage, J. L. Hicks, B. van Balken, T. W. Aalders, J. A. Schalken, and A. M. De Marzo Intermediate Cells in Human Prostate Epithelium Are Enriched in Proliferative Inflammatory Atrophy Am. J. Pathol., May 1, 2003; 162(5): 1529 - 1537. [Abstract] [Full Text] [PDF]

				S. M. Lippman and W. K. Hong Cancer Prevention Science and Practice Cancer Res., September 15, 2002; 62(18): 5119 - 5125. [Full Text] [PDF]

				T. Ernst, M. Hergenhahn, M. Kenzelmann, C. D. Cohen, M. Bonrouhi, A. Weninger, R. Klaren, E. F. Grone, M. Wiesel, C. Gudemann, et al. Decrease and Gain of Gene Expression Are Equally Discriminatory Markers for Prostate Carcinoma : A Gene Expression Analysis on Total and Microdissected Prostate Tissue Am. J. Pathol., June 1, 2002; 160(6): 2169 - 2180. [Abstract] [Full Text] [PDF]

				J. Luo, S. Zha, W. R. Gage, T. A. Dunn, J. L. Hicks, C. J. Bennett, C. M. Ewing, E. A. Platz, S. Ferdinandusse, R. J. Wanders, et al. {alpha}-Methylacyl-CoA Racemase: A New Molecular Marker for Prostate Cancer Cancer Res., April 1, 2002; 62(8): 2220 - 2226. [Abstract] [Full Text] [PDF]