Chemoprevention of colorectal cancer by inhibition of cyclooxygenase-2 derived prostaglandin E2 signaling: Recent advances in basic biology
- 31 Downloads
Experimental evidence collected over the past decade has revealed that targeting cyclooxygenase-2 (COX-2) may have some efficacy for chemoprevention of cancer. However, recent safety concerns over the long-term use of COX-2 selective inhibitors are prompting research aimed at identifying other specific targets downstream of COX-2. In this regard, several groups have found that NSAIDs and COX-2 selective inhibitors primarily reduce the production of prostaglandin (PG) E2, a biologically active lipid product of the COX-2 enzyme, which results in attenuation of PGE2 signaling in the tumor microenvironment. Therefore, a detailed understanding of the PGE2 signaling pathway in transformed cells is critical to help identify novel and safer targets for effective prevention and/or treatment of cancer. Here we review the recent advances in elucidating the molecular mechanisms by which PGE2 promotes carcinogenesis.
Unable to display preview. Download preview PDF.
References and Recommended Reading
- 2.Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 2005, 50:7–33.Google Scholar
- 27.Hansen-Petrik MB, McEntee MF, Jull B, et al.: Prostaglandin E(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min+) mice. Cancer Res 2002, 62:403–408. Direct evidence that PGE2 is the main prostaglandin responsible for promoting growth of intestinal tumor.PubMedGoogle Scholar
- 30.Sonoshita M, Takaku K, Sasaki N, et al.: Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nature Medicine 2001, 7:1048–1051. First genetic evidence that EP2 receptor can promote intestinal tumorigenesis downstream of COX-2.PubMedCrossRefGoogle Scholar
- 44.Shao J, Jung C, Liu C, Sheng H: Prostaglandin E2 stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer. J Biol Chem 2005, 280:26565–26572. Along with Castellone et al. , this article shows that mitogenic effects of PGE2 on colon cancer cells are dependent on interaction between PGE2 and Wnt signaling.PubMedCrossRefGoogle Scholar
- 45.Castellone MD, Teramoto H, Williams BO, et al.: Prostaglandin E2 promotes colon cancer cell growth through a novel Gs-axin-β-catenin signaling axis. Science 2005, 310:1504–1510. Along with Shao et al. , this article shows that mitogenic effects of PGE2 on colon cancer cells are dependent on interaction between PGE2 and Wnt signaling.PubMedCrossRefGoogle Scholar