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.

Gastroenterology
|October 1, 1994
PubMed
Abstract

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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