Prostaglandin E2 promotes the nuclear accumulation of lymphoid enhancer factor-1 in poorly differentiated breast cancer cells.
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.
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
Ioannis
I
Stasinopoulos
Tiffany
T
Greenwood
Kristine
K
Glunde
Zaver M
ZM
Bhujwalla
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000502:physiology*; D005260:Female; D020868:Gene Silencing; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D051176:beta Catenin / Q000378:metabolism
C495267:CTNNB1 protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051176:beta Catenin; D051546:Cyclooxygenase 2; D015232:Dinoprostone