Accession Number:
ADA495776
Title:
Discovery and Role of a Novel Eicosanoid Family in Breast Cancer
Descriptive Note:
Annual rept. 1 Aug 2007-31 Jul 2008
Corporate Author:
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
Personal Author(s):
Report Date:
2007-08-01
Pagination or Media Count:
7.0
Abstract:
There is strong evidence for the induction of the pro-inflammatory enzymes 5-lipoxygenase 5-LOX and cyclooxygenase-2 COX-2 in many types of cancer, including breast cancer. Upregula-tion of both enzymes is associated with promoting tumorigenesis and a negative prognosis of the disease. The 5-LOX leukotriene and COX-2 prostaglandin pathways have traditionally been viewed as independent biosynthetic routes to eicosanoid lipid hormones, yet recent enzy-mological analyses establish that the 5-LOX product, 5-HETE, is an excellent COX-2 substrate, forming a novel double endoperoxide product that has the potential to evolve into a novel family of biomediators. In this funding period we have used LC-MS to detect two cellular metabolites that were derived from the novel di-endoperoxide product. The metabolites are similar in molecular weight to the parent di-endoperoxide, and their formation is blocked by presence of the COX-2 inhibitor indomethacin. Detection of these products is a major step forward in establishing a potential novel eicosanoid-forming pathway resulting from the cross-over of the leukotriene and prostaglandin pathways in breast cancer.
Descriptors:
Subject Categories:
- Medicine and Medical Research