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 Citations (Scopus)

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

Fingerprint

Cyclooxygenase 2
Dinoprostone
Breast Neoplasms
Epoprostenol
Blood Vessels
Breast
Endothelial Cells
Therapeutics
Breast Diseases
Carcinoma in Situ
Vascular Endothelium
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Neoplasms
Up-Regulation
Epithelial Cells
Prostaglandin-E Synthases
Cell Line
Enzymes

Keywords

  • Breast cancer
  • Cyclooxygenase
  • Microsomal prostaglandin E synthase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Microsomal prostaglandin E2 synthase-1 in breast cancer : A potential target for therapy. / Mehrotra, Sanjana; Morimiya, Akira; Agarwal, Beamon; Konger, Raymond; Badve, Sunil.

In: Journal of Pathology, Vol. 208, No. 3, 01.02.2006, p. 356-363.

Research output: Contribution to journalArticle

Mehrotra, Sanjana ; Morimiya, Akira ; Agarwal, Beamon ; Konger, Raymond ; Badve, Sunil. / Microsomal prostaglandin E2 synthase-1 in breast cancer : A potential target for therapy. In: Journal of Pathology. 2006 ; Vol. 208, No. 3. pp. 356-363.
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