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Prostaglandin EP receptors: Targets for treatment and prevention of colorectal cancer?
Mark A. Hull, Stanley C.W. Ko and Gillian Hawcroft
Mol Cancer Ther 2004;3:1031-1039.

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Molecular Cancer Therapeutics

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Prostaglandin EP receptors: Targets for treatment and prevention of colorectal cancer?
Mark A. Hull, Stanley C.W. Ko, and
Gillian Hawcroft
Molecular Medicine Unit, University of Leeds, St. James’s
University Hospital, Leeds, United Kingdom

Abstract
The importance of the prostaglandin (PG) synthesis pathway, particularly the rate-limiting enzymatic step catalyzed by cyclooxygenase, to colorectal carcinogenesis and development of novel anticolorectal cancer therapy is well established. The predominant PG species in benign and malignant colorectal tumors is PGE2. PGE2 acts via four
EP receptors termed EP1 to EP4. Recently, EP receptors have been identified as potential targets for treatment and/ or prevention of colorectal cancer. This review summarizes existing knowledge of the expression and function of the EP receptor subtypes in human and rodent intestine during tumorigenic progression and describes the current literature on targeting EP receptor signaling during intestinal tumorigenesis. [Mol Cancer Ther 2004;3(8):1031 – 9]

The Prostaglandin Synthesis Pathway during
Colorectal Carcinogenesis
The importance of the prostaglandin (PG) synthesis pathway (Fig. 1) as a potential target for treatment and/ or prevention of colorectal cancer is well established (1, 2).
The rate-limiting step of the PG pathway is catalyzed by the cyclooxygenase (COX) enzyme, whereby arachidonic acid is converted to an unstable PG endoperoxide intermediate
PGH2 (Fig. 1). PGH2 is converted to a series of different PGs dependent on the profile of specific PG synthases present in a particular cell or tissue (Fig. 1; ref. 3). PGs have a relatively short half-life and are believed to act over short distances in an autocrine or paracrine manner via specific cell surface and/or nuclear receptors (3). There are five classes of cell surface PG receptors corresponding to the

Received 3/3/04; revised 5/12/04; accepted 5/26/04.
Grant support: Medical Research Council (United Kingdom) and Yorkshire
Cancer Research (M. Hull) and Association for International Cancer
Research (G. Hawcroft).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Requests for reprints: Mark A. Hull, Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St. James’s University Hospital,
Leeds LS9 7TF, United Kingdom. Phone: 44-113-206-5251;
Fax: 44-113-242-9722. E-mail: M.A.Hull@leeds.ac.uk
Copyright C 2004 American Association for Cancer Research.

main PG species termed EP, DP, FP, IP, and TP (Fig. 1; ref. 3). In addition, nuclear peroxisome proliferatoractivated receptors y and g are…