Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors.
OBJECTIVE
Multiple studies show that continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the risk of colon cancer in humans and carcinogen-treated rodents. One target for NSAIDs is cyclooxygenase (COX), and two isoforms of this enzyme have been identified: COX-1 and COX-2. The present study was undertaken to determine if there is differential expression of COX in colonic tumors in azoxymethane-treated rats.


METHODS
COX-1 and COX-2 messenger RNA levels were determined by Northern blot analysis of total RNA isolated from colonic tumors and normal adjacent mucosa. COX-2 protein levels were determined by Western blotting analysis. Quantitation of relative band densities was performed using standard densitometry scanning techniques.


RESULTS
There was a marked increase in COX-2 RNA levels in six of six colonic tumors compared with paired normal mucosa. In contrast, there was equivalent intensity of the COX-1 RNA transcript between the normal mucosa and tumor in all of the specimens examined. Western blotting analysis showed an increase in the level of the COX-2 protein in four of five of the colonic tumor samples.


CONCLUSIONS
COX-2 but not COX-1 gene expression is markedly elevated in most colonic tumors examined in azoxymethane-treated rodents. COX-2 may provide a target for chemopreventive strategies for colorectal cancer.
DuBois
R N
RN
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Radhika
A
A
Reddy
B S
BS
Entingh
A J
AJ
D000818:Animals; D001397:Azoxymethane; D015152:Blotting, Northern; D015153:Blotting, Western; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D051546:Cyclooxygenase 2; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D007527:Isoenzymes; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001397:Azoxymethane