Up-regulation of Cyclooxygenase 2 Gene Expression in Human Colorectal Adenomas and Adenocarcinomas

Gastroenterology. 1994 Oct;107(4):1183-8. doi: 10.1016/0016-5085(94)90246-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenoma / genetics*
  • Adult
  • Aged
  • Base Sequence
  • Blotting, Northern
  • Colorectal Neoplasms / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Isoenzymes / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotide Probes / genetics
  • Prostaglandin-Endoperoxide Synthases / genetics*

Substances

  • Isoenzymes
  • Oligonucleotide Probes
  • Prostaglandin-Endoperoxide Synthases