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Perspectives
Wnt and Cyclooxygenase-2 Cross-talk Accelerates Adenoma Growth
Dingzhi Wang, Jason R. Mann and Raymond N. DuBois
volume 3 | issue 12
december 2004Pages: 1512 - 1515
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Both Wnt and cyclooxygenase (COX-2) pathways are activated in most sporadic and familial colorectal cancers, especially in those with chromosomal instability. We have recently shown that a common target of both signaling pathways, the peroxisome proliferator-activated receptor (PPAR)-?, is involved in intestinal adenoma growth. Activation of this receptor by synthetic agonist (GW501516) or COX-2-derived prostaglandin E2 (PGE2) accelerates intestinal adenoma growth in ApcMin mice. Moreover, these effects are lost in ApcMin mice lacking PPAR?. These findings implicate PPAR? as a focal point of cross-talk between the Wnt and prostaglandin signaling pathways. Based on this work it looks as if PPAR? agonists currently in development for treatment of dyslipidemias and obesity may increase the risk of tumor formation in humans. By contrast, antagonists of PPAR? may provide a novel approach for prevention and treatment of colorectal cancer.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.