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Relationships of Prostaglandin E 2 with Fatty Acid Concentrations and Gene Expression in Colon of Individuals at Increased Risk of Colon Cancer
Author(s) -
Sidahmed Elkhansa,
Sen Ananda,
Ren Jianwei,
Turgeon Kim,
Ruffin Mack,
Brenner Dean,
Djuric Zora
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.753.9
Subject(s) - colorectal cancer , gene , gene expression , medicine , gastroenterology , cancer research , prostaglandin , cancer , oncology , chemistry , biochemistry
PGE 2 is a well‐known biomarker for colon cancer risk. PGE 2 is formed from arachidonic acid (AA) via cyclooxygenases (COX‐1 and 2) and prostaglandin E synthases (PGES), whereas it is catabolized by15‐PG dehydrogenase (HPGD). The objective was to understand inter‐individual differences in PGE 2 concentrations by evaluating the impact of substrate availability and expression of genes in the PGE 2 pathway. Colon biopsies were obtained from individuals at high risk for colon cancer. Quantitative Real Time PCR was used to measure mRNA expression of genes in the PGE 2 pathway: COX‐1 and 2, PGES‐1 and 3, HPGD and PGE 2 receptors 2 and 4. The most expressed genes were HPGD and COX‐1. COX‐1 was positively associated with PGE 2 . There was no association of PGE 2 with the substrate AA or eicosapentaneoic acid. Saturated fatty acid (SFA), however, was positively associated with PGE 2, and there was a trend for a negative association with monounsaturated fatty acids. The mechanism involved for the effects of SFA, a non‐substrate fatty acid, on PGE 2 production could involve the activation of toll‐like receptors that in turn activate COX‐1 or the allosteric regulation of COX‐1 by SFA. Both SFA and COX‐1 were significant positive predictors of PGE 2 after controlling for NSAID use. These results are consistent with the targeting of COX‐1 for colon cancer prevention in individuals at high risk. This differs from data supporting COX‐2 as a target for prevention on animal models of colon carcinogenesis. Supported by NIH grant grants CA120381 and CA130810