[PDF][PDF] Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ

D Wang, H Wang, Q Shi, S Katkuri, W Walhi… - Cancer cell, 2004 - cell.com
D Wang, H Wang, Q Shi, S Katkuri, W Walhi, B Desvergne, SK Das, SK Dey, RN DuBois
Cancer cell, 2004cell.com
Cyclooxygenase-derived prostaglandin E 2 (PGE 2) is the predominant prostanoid found in
most colorectal cancers (CRC) and is known to promote colon carcinoma growth and
invasion. However, the key downstream signaling pathways necessary for PGE 2-induced
intestinal carcinogenesis are unclear. Here we report that PGE 2 indirectly transactivates
PPARδ through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma
formation. We also found that PGE 2 treatment of Apc min mice dramatically increased …
Abstract
Cyclooxygenase-derived prostaglandin E2 (PGE2) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE2-induced intestinal carcinogenesis are unclear. Here we report that PGE2 indirectly transactivates PPARδ through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE2 treatment of Apcmin mice dramatically increased intestinal adenoma burden, which was negated in Apcmin mice lacking PPARδ. We demonstrate that PPARδ is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.
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