Open AccessDelta‐6‐desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue
Author(s) -
PenderCudlip Marilla C.,
Krag Karen J.,
Martini David,
Yu Jeanne,
Guidi Anthony,
Skinner Sandy S.,
Zhang Yu,
Qu Xiying,
He Chengwei,
Xu Yi,
Qian Steven Y.,
Kang Jing X.
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12129
Subject(s) - arachidonic acid , breast cancer , linoleic acid , medicine , endocrinology , cancer , prostaglandin , chemistry , biology , enzyme , biochemistry , fatty acid
Omega‐6 (n‐6) arachidonic acid ( AA ) and its pro‐inflammatory metabolites, including prostaglandin E 2 ( PGE 2 ), are known to promote tumorigenesis. Delta‐6 desaturase ( D 6 D ) is the rate‐limiting enzyme for converting n‐6 linoleic acid ( LA ) to AA . Our objective was to determine if AA synthesis, specifically D 6 D activity, and PGE 2 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 2 levels. Lipid analysis revealed higher levels of LA metabolites ( C 18:3 n‐6, C 20:3 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 D 6 D 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 2 levels were increased in cancerous tissue, particularly in ER − patients. The results showed that the endogenous AA synthetic pathway, D 6 D activity, and PGE 2 levels are increased in breast tumors, particularly those of the ER − genotype. These findings suggest that the AA synthetic pathway and the D 6 D 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.