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Updated: May 11, 2026

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Published on: May 17, 2013
Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas
C E Eberhart1, R J Coffey, A Radhika
1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Background/Aims:
Several clinical, epidemiological, and animal studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may alter the incidence of colorectal cancer. A likely target for NSAIDs is cyclooxygenase, a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified; cyclooxygenase (COX) 1 and COX-2. The present study was undertaken to determine if there is differential expression of these isoforms in colorectal neoplasia, and, if so, at what stage in malignant transformation this occurs.
Methods:
COX-1 and COX-2 messenger RNA (mRNA) levels were determined by Northern blot analysis of poly(A)+ RNA isolated from human colorectal cancers, adenomas, and accompanying normal mucosa.
Results:
There was a marked increase in COX-2 mRNA levels in 12 of 14 carcinomas (86%) compared with paired normal mucosa. In contrast, there was equivalent intensity of the COX-1 mRNA transcript between the normal mucosa and cancer in all 14 cases. In six pairs of colorectal adenomas and normal mucosa, three showed up-regulation of COX-2 in the adenoma compared with the normal mucosa. Because COX-2 expression is low to undetectable in normal colorectal mucosa, 14 unpaired adenomas were examined for COX-2 expression; a clearly detectable transcript was identified in six (43%).
Conclusions:
COX-2, but not COX-1, gene expression is markedly elevated in most human colorectal cancers compared with accompanying normal mucosa. Furthermore, COX-2 expression seems to be increased in a subset of adenomas. COX-2 may provide an attractive therapeutic target in colorectal neoplasia.
Insights
Cyclooxygenase-2 (COX-2) gene expression is significantly elevated in most colorectal cancers and some adenomas, unlike COX-1. This suggests COX-2 is a potential therapeutic target for colorectal neoplasia.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may influence colorectal cancer incidence.
- Cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2, are implicated in arachidonic acid metabolism and cancer development.
- Differential expression of COX isoforms in colorectal neoplasia requires investigation.
Purpose of the Study:
- To investigate the differential expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human colorectal neoplasia.
- To determine at which stage of malignant transformation COX-2 expression is altered.
Main Methods:
- Messenger RNA (mRNA) levels for COX-1 and COX-2 were quantified using Northern blot analysis.
- Analysis was performed on RNA extracted from human colorectal cancers, adenomas, and adjacent normal mucosa.
Main Results:
- COX-2 mRNA levels were markedly increased in 86% of colorectal carcinomas compared to normal mucosa.
- COX-1 mRNA levels remained consistent between normal mucosa and cancerous tissue.
- COX-2 expression was also found to be up-regulated in a subset of colorectal adenomas.
Conclusions:
- Cyclooxygenase-2 (COX-2) gene expression is significantly elevated in the majority of human colorectal cancers.
- Increased COX-2 expression is also observed in a portion of colorectal adenomas.
- COX-2 represents a promising therapeutic target for colorectal neoplasia.
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