Related Experiment Video
Updated: Aug 14, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Microsomal prostaglandin E2 synthase-1 in breast cancer: a potential target for therapy
Sanjana Mehrotra1, Akira Morimiya, Beamon Agarwal
1Department of Pathology, Indiana University, Indianapolis, Indiana 46202, USA.
Abstract:
The anti-tumour actions of cyclooxygenases (COX) are thought to be mediated by inhibition of prostaglandin E(2) (PGE(2)) synthesis. However, COX-2 inhibition also alters cellular production of other prostaglandins such as prostacyclin (PGI(2)). The latter action is believed to be important for the development of adverse cardio-vascular events. Microsomal PGES (mPGES-1) is an enzyme downstream to COX-2 and affects PGE(2) production only. It is possible that targeting mPGES-1 could decrease PGE(2) production without affecting PGI(2) production. In order to assess the potential of mPGES-1 as a target for therapy, we analysed its expression in breast cell lines and normal and malignant breast tissues. The expression of mPGES-1 and COX-2 was correlated in tumour cells and vascular endothelium, and with prognostic parameters in breast cancer. Although not detectable in normal epithelial cells, expression was noted in areas of fibrocystic change and in situ carcinoma. mPGES-1 expression was noted in 79% of breast cancer tissues. Its expression did not correlate with COX-2 overexpression or with prognostic markers of breast cancer. Endothelial cells did not show mPGES-1 expression. Upregulation of mPGES-1 is therefore frequent in pre-malignant and malignant breast disease. In this study, coordinate over-expression of COX-2 and mPGES-1 was not observed, particularly in the endothelial cells of blood vessels. Targeting mPGES-1 might prove to be an alternative therapeutic strategy to inhibit PGE2 production.
Insights
Targeting microsomal prostaglandin E synthase-1 (mPGES-1) may offer a safer way to reduce prostaglandin E2 (PGE2) in breast cancer. This enzyme’s upregulation in pre-malignant and malignant breast tissues suggests its therapeutic potential.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Cyclooxygenase (COX) inhibition reduces prostaglandin E2 (PGE2) but can increase cardiovascular risks by affecting prostacyclin (PGI2).
- Microsomal prostaglandin E synthase-1 (mPGES-1) is a downstream enzyme solely responsible for PGE2 production.
- Targeting mPGES-1 could selectively inhibit PGE2 without impacting PGI2, potentially mitigating adverse cardiovascular effects.
Purpose of the Study:
- To investigate the expression of mPGES-1 in breast cell lines and tissues.
- To correlate mPGES-1 expression with COX-2 expression and breast cancer prognostic markers.
- To evaluate mPGES-1 as a potential therapeutic target for breast cancer treatment.
Main Methods:
- Analysis of mPGES-1 and COX-2 expression in breast cell lines and normal/malignant breast tissues.
- Correlation analysis of mPGES-1 expression with COX-2 levels and prognostic parameters.
- Immunohistochemical assessment of mPGES-1 in various breast tissue types.
Main Results:
- mPGES-1 was not detected in normal epithelial cells but was present in fibrocystic changes and in situ carcinoma.
- mPGES-1 was expressed in 79% of breast cancer tissues.
- mPGES-1 expression did not correlate with COX-2 overexpression or prognostic markers; endothelial cells lacked mPGES-1 expression.
Conclusions:
- mPGES-1 is frequently upregulated in pre-malignant and malignant breast disease.
- The lack of coordinate overexpression with COX-2, especially in vascular endothelium, supports its potential as a selective therapeutic target.
- Targeting mPGES-1 represents a promising alternative strategy for inhibiting PGE2 production in breast cancer therapy.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
02:38Mitogens and the Cell Cycle
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...