CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 GENE-EXPRESSION IN HUMAN COLORECTAL ADENOCARCINOMAS AND IN AZOXYMETHANE-INDUCED COLONIC TUMORS IN RATS

Increased prostaglandin E(2) synthesis is considered important in both human and experimental colon carcinogenesis. It is not known, however , which cyclooxygenase isoenzyme is involved. The aim of this study wa s to compare the content of mRNA for cyclooxygenase-1 and cyclooxygena se-2 in colorectal cancers with the content in normal colonic specimen s. Fifteen human colorectal adenocarcinomas, 35 azoxymethane induced c olonic tumours from rats, and specimens of normal colon were analysed by reverse transcription and polymerase chain reaction (RT-PCR). It wa s found that cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in azoxymethane induced colonic tumours, compared with specimens take n adjacent to the tumours or from the macroscopically normal intestine distant from the tumours. Cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in specimens from the macroscopically normal intestine of azoxymethane treated animals, compared with colonic specimens from saline treated rats. Cyclooxygenase-2 mRNA, but not cyclooxygenase-1 m RNA, was increased in human colorectal compared with the adjacent or m acroscopically normal mucosa distant from the tumours. The results sug gest that cyclooxygenase-2 is involved in the increased prostaglandin E(2) synthesis in colonic cancers, and that activation of this isoenzy me is an early event in colon carcinogenesis. However, cyclooxygenase- 1 may also be involved, at least in experimental colon carcinogenesis.