Carcinogenesis, Vol 19, 905-910, Copyright © 1998 by Oxford University Press
AF Badawi, A El-Sohemy, LL Stephen, AK Ghoshal and MC Archer
Dietary n-6 polyunsaturated fatty acids (PUFAs) promote rat mammary cancer
while n-3 PUFAs are inhibitory. The purpose of this study was to determine
whether the fats exert their effects by altering the expression of genes
that affect cancer development. Therefore, we have examined the effect of
PUFAs on the expression of the cyclooxygenase (COX) 1 and 2 genes that are
involved in prostaglandin biosynthesis. We also investigated the effect of
dietary PUFAs on the expression of the p21ras protein and Ha-ras mRNA. Rats
were fed either low- (7%; LF) or high- (21%; HF) fat diets that were rich
in either n-6 PUFAs (safflower oil, S) or n-3 PUFAs (menhaden oil, M) for 3
weeks. COX-1 mRNA levels were approximately the same in groups fed diets
containing either level of menhaden oil, but were increased by
approximately 30% in the LFS and HFS groups (P < 0.05). Transcripts of
the inducible COX-2 gene were not detectable in the menhaden oil groups,
but this gene was expressed in animals fed either level of safflower oil
and in the HFS group was associated with increased levels of COX enzymatic
activity and production of PGE2. Animals fed safflower oil had elevated
levels of p21ras protein compared to animals fed menhaden oil. Ha-ras mRNA
was increased by approximately 35% in animals fed HFS compared to the group
fed HFM (P < 0.05). These results demonstrate that dietary n-6 PUFAs
upregulate COX-2 and, to some extent, COX-1 expression. There was a
concomitant increase in COX enzyme activity and PG synthesis in the mammary
glands of rats fed high levels of n-6 PUFAs. Together with associated
changes in p21ras expression, these results may explain, at least in part,
the promoting effects of dietary n-6 PUFAs on mammary carcinogenesis.
ARTICLES
The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Age-Related Eye Disease Study Research Group The Relationship of Dietary Lipid Intake and Age-Related Macular Degeneration in a Case-Control Study: AREDS Report No. 20 Arch Ophthalmol, May 1, 2007; 125(5): 671 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Reese, J. D. Anderson, N. Brown, C. Roman, and R. I. Clyman Inhibition of cyclooxygenase isoforms in late- but not midgestation decreases contractility of the ductus arteriosus and prevents postnatal closure in mice Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1717 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Degner, M. Q. Kemp, G. T. Bowden, and D. F. Romagnolo Conjugated Linoleic Acid Attenuates Cyclooxygenase-2 Transcriptional Activity via an Anti-AP-1 Mechanism in MCF-7 Breast Cancer Cells J. Nutr., February 1, 2006; 136(2): 421 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L.E. Siezen, A. I.M. van Leeuwen, N. R. Kram, M. E.M. Luken, H. J. van Kranen, and E. Kampman Colorectal adenoma risk is modified by the interplay between polymorphisms in arachidonic acid pathway genes and fish consumption Carcinogenesis, February 1, 2005; 26(2): 449 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Calviello, F. Di Nicuolo, S. Gragnoli, E. Piccioni, S. Serini, N. Maggiano, G. Tringali, P. Navarra, F. O. Ranelletti, and P. Palozza n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1{alpha} induction pathway Carcinogenesis, December 1, 2004; 25(12): 2303 - 2310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C Larsson, M. Kumlin, M. Ingelman-Sundberg, and A. Wolk Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms Am. J. Clinical Nutrition, June 1, 2004; 79(6): 935 - 945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Badawi, M. B. Eldeen, Y. Liu, E. A. Ross, and M. Z. Badr Inhibition of Rat Mammary Gland Carcinogenesis by Simultaneous Targeting of Cyclooxygenase-2 and Peroxisome Proliferator-activated Receptor {gamma} Cancer Res., February 1, 2004; 64(3): 1181 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Nathoo, G H Barnett, and M Golubic The eicosanoid cascade: possible role in gliomas and meningiomas J. Clin. Pathol., January 1, 2004; 57(1): 6 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tardieu, J.-P. Jaeg, A. Deloly, D. E. Corpet, J. Cadet, and C. R. Petit The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates apoptosis in mucosa during early colonic inflammation in rats Carcinogenesis, May 1, 2000; 21(5): 973 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Inano, M. Onoda, N. Inafuku, M. Kubota, Y. Kamada, T. Osawa, H. Kobayashi, and K. Wakabayashi Chemoprevention by curcumin during the promotion stage of tumorigenesis of mammary gland in rats irradiated with {gamma}-rays Carcinogenesis, June 1, 1999; 20(6): 1011 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Liu, S.-H. Chang, K. Narko, O. C. Trifan, M.-T. Wu, E. Smith, C. Haudenschild, T. F. Lane, and T. Hla Overexpression of Cyclooxygenase-2 Is Sufficient to Induce Tumorigenesis in Transgenic Mice J. Biol. Chem., May 18, 2001; 276(21): 18563 - 18569. [Abstract] [Full Text] [PDF]
|
|