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.
Original language | English (US) |
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Pages (from-to) | 9-14 |
Number of pages | 6 |
Journal | Prostaglandins and Other Lipid Mediators |
Volume | 99 |
Issue number | 1-2 |
DOIs | |
State | Published - Oct 2012 |
Keywords
- Breast cancer
- COX-2
- Cyclooxygenase-2
- Inflammation
- LEF-1
- Lymphoid enhancer factor-1
- PGE
- Prostaglandin E
- Wnt
- β-Catenin
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Pharmacology
- Cell Biology