TY - JOUR
T1 - Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas
AU - Eberhart, Charles E.
AU - Coffey, Robert J.
AU - Radhika, Aramandla
AU - Giardiello, Francis M.
AU - Ferrenbach, Suzanne
AU - Dubois, Raymond N.
PY - 1994/10
Y1 - 1994/10
N2 - 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.
AB - 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.
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U2 - 10.1016/0016-5085(94)90246-1
DO - 10.1016/0016-5085(94)90246-1
M3 - Article
C2 - 7926468
AN - SCOPUS:0027993458
SN - 0016-5085
VL - 107
SP - 1183
EP - 1188
JO - Gastroenterology
JF - Gastroenterology
IS - 4
ER -