| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan [H. T., M. S., H. O., M. O., M. M. T.]; Department of Digestive Surgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan [K-i. S.]; and Laboratory of Experimental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709 [P. C. C., R. L.]
Membrane arachidonic acid is converted by cyclooxygenase (COX) into prostaglandin (PG) G2 and then to PGH2 which is subsequently metabolized to PGE2 by PGE synthase (PGES). Both COX-1 and COX-2 play critical roles in intestinal polyp formation, whereas COX-2 is also expressed in cancers of a variety of organs. Likewise, inducible microsomal PGES (mPGES-1) is expressed in several types of cancer, although its role in benign polyp formation has not been investigated. We demonstrated recently that most COX-2-expressing cells in the polyps are stromal fibroblasts. Here we show colocalization of COX-1, COX-2 and mPGES in the intestinal polyp stromal fibroblasts of Apc
716 mice, a model for familial adenomatous polyposis. Contrary to COX-2 that was induced only in polyps >1 mm in diameter, COX-1 was found in polyps of any size. In polyps >1 mm, not only COX-2 but also mPGES was induced in the stromal fibroblasts where COX-1 had already been expressed. Although polyp number and size were markedly reduced in COX-1 (-/-) or COX-2 (-/-) compound mutant Apc mice, both COX-2 and mPGES were induced in the COX-1 (-/-) polyps, whereas COX-1 was expressed in the COX-2 (-/-) polyps. We found also in human familial adenomatous polyposis polyps that COX-2 and mPGES were induced in the COX-1-expressing fibroblasts. On the basis of these results, we propose that COX-1 expression in the stromal cells secures the basal level of PGE2 that can support polyp growth to 
1 mm, and that simultaneous inductions of COX-2 and mPGES support the polyp expansion beyond 1 mm by boosting the stromal PGE2 production.
This article has been cited by other articles:
|
|
 |
|
  S. J. Baek, M. F. McEntee, and A. M. Legendre REVIEW PAPER: Cancer Chemopreventive Compounds and Canine Cancer Vet. Pathol., July 1, 2009; 46(4): 576 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Warren, K. J. Paulhill, L. A. Davidson, J. R. Lupton, S. S. Taddeo, M. Y. Hong, R. J. Carroll, R. S. Chapkin, and N. D. Turner Quercetin May Suppress Rat Aberrant Crypt Foci Formation by Suppressing Inflammatory Mediators That Influence Proliferation and Apoptosis J. Nutr., January 1, 2009; 139(1): 101 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Howe and S. M. Lippman Modulation of Breast Cancer Risk by Nonsteroidal Anti-inflammatory Drugs J Natl Cancer Inst, October 15, 2008; 100(20): 1420 - 1423. [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Halberg, M. C. Larsen, T. L. Elmergreen, A. Y. Ko, A. A. Irving, L. Clipson, and C. R. Jefcoate Cyp1b1 Exerts Opposing Effects on Intestinal Tumorigenesis via Exogenous and Endogenous Substrates Cancer Res., September 15, 2008; 68(18): 7394 - 7402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakanishi, D. C. Montrose, P. Clark, P. R. Nambiar, G. S. Belinsky, K. P. Claffey, D. Xu, and D. W. Rosenberg Genetic Deletion of mPGES-1 Suppresses Intestinal Tumorigenesis Cancer Res., May 1, 2008; 68(9): 3251 - 3259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yu, J. Fan, Y. Hui, C. A. Rouzer, L. J. Marnett, A. J. Klein-Szanto, G. A. FitzGerald, and C. D. Funk Targeted Cyclooxygenase Gene (Ptgs) Exchange Reveals Discriminant Isoform Functionality J. Biol. Chem., January 12, 2007; 282(2): 1498 - 1506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kohno, M. Momoi, M. L. Oo, J.-H. Paik, Y.-M. Lee, K. Venkataraman, Y. Ai, A. P. Ristimaki, H. Fyrst, H. Sano, et al. Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation. Mol. Cell. Biol., October 1, 2006; 26(19): 7211 - 7223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.A. Hull, O.O. Faluyi, C.W.S. Ko, S. Holwell, D.J. Scott, R.J. Cuthbert, R. Poulsom, R. Goodlad, C. Bonifer, A.F. Markham, et al. Regulation of stromal cell cyclooxygenase-2 in the ApcMin/+ mouse model of intestinal tumorigenesis Carcinogenesis, March 1, 2006; 27(3): 382 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kanda, H. Seno, M. Kawada, T. Sawabu, Y. Uenoyoma, T. Nakajima, Y. Konda, H. Fukui, T. Takeuchi, and T. Chiba Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G519 - G527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ju, J. Hong, J.-n. Zhou, Z. Pan, M. Bose, J. Liao, G.-y. Yang, Y. Y. Liu, Z. Hou, Y. Lin, et al. Inhibition of Intestinal Tumorigenesis in Apcmin/+ Mice by (-)-Epigallocatechin-3-Gallate, the Major Catechin in Green Tea Cancer Res., November 15, 2005; 65(22): 10623 - 10631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Howe, S.-H. Chang, K. C. Tolle, R. Dillon, L. J.T. Young, R. D. Cardiff, R. A. Newman, P. Yang, H. T. Thaler, W. J. Muller, et al. HER2/neu-Induced Mammary Tumorigenesis and Angiogenesis Are Reduced in Cyclooxygenase-2 Knockout Mice Cancer Res., November 1, 2005; 65(21): 10113 - 10119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, T.-o Ishikawa, M. Oshima, and M. M. Taketo The Threshold Level of Adenomatous Polyposis Coli Protein for Mouse Intestinal Tumorigenesis Cancer Res., October 1, 2005; 65(19): 8622 - 8627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rigas and K. Kashfi Cancer Prevention: A New Era beyond Cyclooxygenase-2 J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Blaine, A. M. Meyer, G. Hurteau, M. Wick, J. A. Hankin, R. C. Murphy, A. J. Dannenberg, M. W. Geraci, K. Subbaramaiah, and R. A. Nemenoff Targeted over-expression of mPGES-1 and elevated PGE2 production is not sufficient for lung tumorigenesis in mice Carcinogenesis, January 1, 2005; 26(1): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. T. Soumaoro, H. Uetake, T. Higuchi, Y. Takagi, M. Enomoto, and K. Sugihara Cyclooxygenase-2 Expression: A Significant Prognostic Indicator for Patients With Colorectal Cancer Clin. Cancer Res., December 15, 2004; 10(24): 8465 - 8471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Moran, D. H. Hunt, S. H. Javid, M. Redston, A. M. Carothers, and M. M. Bertagnolli Apc Deficiency Is Associated with Increased Egfr Activity in the Intestinal Enterocytes and Adenomas of C57BL/6J-Min/+ Mice J. Biol. Chem., October 8, 2004; 279(41): 43261 - 43272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Simmons, R. M. Botting, and T. Hla Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition Pharmacol. Rev., September 1, 2004; 56(3): 387 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kamei, K. Yamakawa, Y. Takegoshi, M. Mikami-Nakanishi, Y. Nakatani, S. Oh-ishi, H. Yasui, Y. Azuma, N. Hirasawa, K. Ohuchi, et al. Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1 J. Biol. Chem., August 6, 2004; 279(32): 33684 - 33695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hull, S. C.W. Ko, and G. Hawcroft Prostaglandin EP receptors: Targets for treatment and prevention of colorectal cancer? Mol. Cancer Ther., August 1, 2004; 3(8): 1031 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Zeytin, A. C. Patel, C. J. Rogers, D. Canter, S. D. Hursting, J. Schlom, and J. W. Greiner Combination of a Poxvirus-Based Vaccine with a Cyclooxygenase-2 Inhibitor (Celecoxib) Elicits Antitumor Immunity and Long-Term Survival in CEA.Tg/MIN Mice Cancer Res., May 15, 2004; 64(10): 3668 - 3678. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
