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Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue
Pender-Cudlip M.C.3; Krag K.J.1; Martini D.1; Yu J.1; Guidi A.4; Skinner S.S.4; Zhang Y.3; Qu X.3; He C.3; Xu Y.2; Qian S.Y.2; Kang J.X.3
2013-06-01
Source PublicationCancer Science
ISSN13479032 13497006
Volume104Issue:6Pages:760-764
Abstract

Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER-) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER- breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P < 0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P < 0.001), and was higher in ER- than in ER+ patients, indicating genotype-related trends. Similarly, PGE levels were increased in cancerous tissue, particularly in ER- patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE levels are increased in breast tumors, particularly those of the ER- genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment. © 2013 Japanese Cancer Association.

DOI10.1111/cas.12129
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000319404600015
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Cited Times [WOS]:34   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorKang J.X.
Affiliation1.Mass General/North Shore Cancer Center
2.North Dakota State University
3.Massachusetts General Hospital
4.North Shore Medical Center
Recommended Citation
GB/T 7714
Pender-Cudlip M.C.,Krag K.J.,Martini D.,et al. Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue[J]. Cancer Science,2013,104(6):760-764.
APA Pender-Cudlip M.C..,Krag K.J..,Martini D..,Yu J..,Guidi A..,...&Kang J.X..(2013).Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue.Cancer Science,104(6),760-764.
MLA Pender-Cudlip M.C.,et al."Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue".Cancer Science 104.6(2013):760-764.
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