Prostaglandin Signaling Stimulates Tumor Growth

Cancer researchers have found that the ability of nonsteroidal anti-inflammatory drugs (NSAIDS) to protect against colorectal cancer (CRC) is at least partially due to inhibition of cyclooxygenase (COX), the enzyme that synthesizes prostaglandin E2 (PGE2), a compound that activates signaling pathways, causing a shift from cell death to cell survival, leading to increased tumor growth.

Investigators at Vanderbilt University (Nashville, TN, USA) worked with a line of mice that were prone to the development of intestinal and rectal polyps. They reported in the September 2004 issue of Cancer Cell that treatment of the animals with PGE2 caused an increase in polyp number and size. The effect of PGE2 was linked to activation of the cell apoptosis regulator peroxisome proliferator-activated receptor d (PPARd). Mice genetically engineered to lack PPARd did not show increased polyp formation after PGE2 treatment.

"Our results identify PPARd as a critical downstream mediator in PGE2-stimulated promotion of colorectal tumor growth,” said senior author Dr. Raymond N. DuBois, professor of medicine at Vanderbilt University. "They suggest that PPARd is an important pro-cancer factor in CRC, and that agents which stimulate PPARd may encourage abnormal cell growth in certain populations at risk for CRC. In addition, it is possible that blocking PPARd might prove useful for prevention and/or treatment of CRC.”



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