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Prostaglandins Other Lipid Mediat. 2012 Oct;99(1-2):9-14. doi: 10.1016/j.prostaglandins.2012.05.002. Epub 2012 May 29.

Prostaglandin E2 promotes the nuclear accumulation of lymphoid enhancer factor-1 in poorly differentiated breast cancer cells.

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1
JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, MD 21205, USA. istasin1@jhmi.edu

Abstract

Products of the COX reaction are frequently elevated in solid tumors and their roles in the malignant phenotype have been extensively investigated. We have shown that COX-2 is essential for the growth of MDA-MB-231 cells in the fat pad of SCID mice and for their extrapulmonary colonization following injection in the tail vein of SCID mice. The molecular changes that follow shRNA-mediated silencing of COX-2 include a significant downregulation of LEF-1, a transcription factor normally activated during development following the Wnt-induced nuclear translocation of β-catenin. We also report that COX-2-silenced cells have reduced nuclear accumulation of LEF-1 protein and that the COX-2 product PGE(2) partially restored nuclear LEF-1 expression in COX-2-silenced cells. Further, we demonstrate that, like parental COX-2 containing MDA-MB-231 cells, COX-2-silenced cells maintain nuclear localization of β-catenin.

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