MECHANISMS OF SIGNAL TRANSDUCTION
Prostaglandin E2 Increases Growth and Motility of Colorectal Carcinoma Cells*

https://doi.org/10.1074/jbc.M009689200Get rights and content
Under a Creative Commons license
open access

Chronic use of nonsteroidal anti-inflammatory drugs results in a significant reduction of risk and mortality from colorectal cancer in humans. All of the mechanism(s) by which nonsteroidal anti-inflammatory drugs exert their protective effects are not completely understood, but they are known to inhibit cyclooxygenase activity. The cyclooxygenase enzymes catalyze a key reaction in the conversion of arachidonic acid to prostaglandins, such as prostaglandin E2 (PGE2). Here we demonstrate that PGE2 treatment of LS-174 human colorectal carcinoma cells leads to increased motility and changes in cell shape. The prostaglandin EP4 receptor signaling pathway appears to play a role in transducing signals which regulate these effects. PGE2 treatment results in an activation of phosphatidylinositol 3-kinase/protein kinase B pathway that is required for the PGE2-induced changes in carcinoma cell motility and colony morphology. Our results suggest that PGE2 might enhance the invasive potential of colorectal carcinoma cells via activation of major intracellular signal transduction pathways not previously reported to be regulated by prostaglandins.

Cited by (0)

Published, JBC Papers in Press, March 12, 2001, DOI 10.1074/jbc.M009689200

*

This work was supported in part by United States Public Health Services Grants RO1DK 47297, P01CA77839, and P30CA-68485 (all to R. N. D.); the T. J. Martell Foundation; and Katie Couric.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a Veterans Administration Research Merit Grant. To whom reprint requests should be addressed: Dept. of Medicine/GI, MCN C-2104, Vanderbilt University Medical Center, 1161 21st Ave. S., Nashville, TN 37232-2279. Tel.: 615-322-5200; Fax: 615-343-6229; E-mail: [email protected].