Reversal of expression of 15-lipoxygenase-1 to cyclooxygenase-2 is associated with development of colonic cancer.
OBJECTIVE
Two different pathways of linoleic acid (LA) metabolism have opposite effects on the development of colonic cancer: a protumoral prostaglandin cascade metabolized by cyclooxygenase (COX)-2, and an antitumoral peroxisome proliferator-activated receptor (PPAR)-gamma ligands metabolized by 15-lipooxygenase (LOX)-1. The aim was to examine the switching of the two LA metabolic pathways in colonic adenomas and carcinomas.


METHODS
The expression of 15LOX-1 mRNA and COX-2 protein was examined in 54 adenomas, 21 pTis carcinoma-in-adenoma lesions and 36 pT3/p Stage II carcinomas of the colon by in-situ hybridization and immunohistochemistry, respectively.


RESULTS
15LOX-1 expression was found in 89% (48 of 54) of adenomas, 43% (nine of 21) of adenomas and 10% (two of 21) of carcinomas in carcinoma-in-adenoma lesions, but not in pT3 carcinomas (P < 0.0001). In contrast, COX-2 production was found in 11% (six of 54) of adenomas, 52% (11 of 21) of adenomas and 71% (15 of 21) of carcinomas in carcinoma-in-adenoma lesions, and 92% (33 of 36) of pT3 carcinomas (P < 0.0001). Concurrence of 15LOX-1 down-regulation and COX-2 up-regulation was found in 6% (three of 54) of adenomas, 33% (seven of 21) of adenomas and 71% (15 of 21) of carcinomas in carcinoma-in-adenoma lesions, and 92% (33 of 36) of pT3 carcinomas (P < 0.0001).


CONCLUSIONS
These results suggest that switching of LA metabolism by reversal of the expression of 15LOX-1 and COX-2 is associated with acquisition of malignant potential in colonic neoplasia.
Yuri
M
M
Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara, Japan.
Sasahira
T
T
Nakai
K
K
Ishimaru
S
S
Ohmori
H
H
Kuniyasu
H
H
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D019787:Linoleic Acid; D001093:Arachidonate 15-Lipoxygenase; D051546:Cyclooxygenase 2