Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats.
Increased prostaglandin E2 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 was to compare the content of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in colorectal cancers with the content in normal colonic specimens. Fifteen human colorectal adenocarcinomas, 35 azoxymethane induced colonic tumours from rats, and specimens of normal colon were analysed by reverse transcription and polymerase chain reaction (RT-PCR). It was found that cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in azoxymethane induced colonic tumours, compared with specimens taken 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 mRNA, was increased in human colorectal cancers, compared with the adjacent mucosa or macroscopically normal mucosa distant from the tumours. The results suggest that cyclooxygenase-2 is involved in the increased prostaglandin E2 synthesis in colonic cancers, and that activation of this isoenzyme is an early event in colon carcinogenesis. However, cyclooxygenase-1 may also be involved, at least in experimental colon carcinogenesis.
Gustafson-Svärd
C
C
Department of Occupational and Environmental Medicine, Faculty of Health Sciences, Linköping University, Sweden.
Lilja
I
I
Hallböök
O
O
Sjödahl
R
R
D000230:Adenocarcinoma / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001397:Azoxymethane; D001483:Base Sequence; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats
D002273:Carcinogens; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases; D001397:Azoxymethane