Abstract A094: mPGES1 deletion increases tumor susceptibility to immune suppression

The pro-tumor contributions of prostaglandin (PG) E 2 are established, as is the clinical efficacy of pharmacological inhibition of COX-2, the rate-limiting enzyme in PGE 2 synthesis. In addition to the desired suppression of tumor PGE 2 , collateral loss of endothelial COX-2-derived PGI 2 imposes a cardiovascular hazard that limits clinical use of COX-2 inhibitors. mPGES1, the terminal enzyme in the PGE 2 synthesis pathway, is an alternative target to interrupt COX-2-driven events in tumors without elevating cardiovascular risk. We engineered mice transgenic for an activated HER2/neu oncogene to lack mPGES1 globally (mPGES1 KO gl ) or only in mammary epithelial cells (mPGES1 KO epi ). Abdominal mammary glands from wild type (WT), heterozygous (het), mPGES1 KO gl , and mPGES1 KO epi mice were harvested at 22 weeks of age, paraffin embedded, HE 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A094.