Transgenic expression of cyclooxygenase-2 in mouse intestine epithelium is insufficient to initiate tumorigenesis but promotes tumor progression.
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.
Al-Salihi
Mazin A
MA
Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Rm 3365, Salt Lake City, UT 84112, USA.
Terrece Pearman
A
A
Doan
Thao
T
Reichert
Ethan C
EC
Rosenberg
Daniel W
DW
Prescott
Stephen M
SM
Stafforini
Diana M
DM
Topham
Matthew K
MK
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D019076:Transgenes
D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
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