Microsomal prostaglandin E2 synthase-1 in breast cancer: A potential target for therapy

Sanjana Mehrotra, Akira Morimiya, Beamon Agarwal, Raymond Konger, Sunil Badve

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

The anti-tumour actions of cyclooxygenases (COX) are thought to be mediated by inhibition of prostaglandin E2 (PGE2) synthesis. However, COX-2 inhibition also alters cellular production of other prostaglandins such as prostacyclin (PGI2). 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 PGE2 production only. It is possible that targeting mPGES-1 could decrease PGE2 production without affecting PGI2 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.

Original languageEnglish (US)
Pages (from-to)356-363
Number of pages8
JournalJournal of Pathology
Volume208
Issue number3
DOIs
StatePublished - Feb 1 2006

Keywords

  • Breast cancer
  • Cyclooxygenase
  • Microsomal prostaglandin E synthase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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