Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas

Charles E. Eberhart, Robert J. Coffey, Aramandla Radhika, Francis M. Giardiello, Suzanne Ferrenbach, Raymond N. Dubois

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    2288 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)1183-1188
    Number of pages6
    JournalGastroenterology
    Volume107
    Issue number4
    DOIs
    StatePublished - Oct 1994

    ASJC Scopus subject areas

    • Hepatology
    • Gastroenterology

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