Journal
CANCER LETTERS
Volume 273, Issue 2, Pages 225-232Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.08.012
Keywords
Cyclooxygenase; Prostaglandin; Colon cancer; Epidermal growth factor receptor; Azoxymethane
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Funding
- Huntsman Cancer Foundation
- R. Harold Burton Foundation
- National institutes of Health [R01-CA95463, P01-CA73992]
- Cancer Center Support [P30 CA042014-20]
- Pre-doctoral Fulbright Award
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We generated mice expressing a COX-2 transgene in colon epithelium and found that they did not develop spontaneous colon tumors. But when treated with azoxymethane, a colon carcinogen, COX-2 mice had a higher tumor load compared to wild-type mice. There was no change in the number of pre-neoplastic lesions, indicating that COX-2 does not affect tumor initiation. Tumors in the COX-2 transgenic mice had higher levels of phosphorylated epidermal growth factor receptor and Akt compared to wild-type mice. Collectively, our data indicate that COX-2 promotes colon tumor progression, but not initiation, and it does so, in part, by activating EGFR and Akt signaling pathways. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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