Leptomycin B, an inhibitor of the nuclear export receptor CRM1, inhibits COX-2 expression. Academic Article uri icon

Overview

abstract

  • Cyclooxygenase (COX)-2, the inducible prostaglandin synthase, is overexpressed in cancer and chronic inflammatory diseases. Post-transcriptional regulation of COX-2 mRNA is important in controlling the expression of the COX-2 gene. Here, we report that leptomycin B (LMB), a specific inhibitor of the nuclear export factor CRM1 potently inhibits the stabilization of COX-2 mRNA in MDA-MB-231 human mammary cancer cells. However, COX-2 promoter-driven reporter gene expression is not inhibited by LMB, suggesting that LMB acts at the post-transcriptional level. Subcellular fractionation experiments indicate that LMB inhibited the time-dependent export of COX-2 mRNA into the membrane-bound polysomal compartment at the endoplasmic reticulum. LMB suppressed COX-2 expression by interleukin-1beta in HT-29 human colon cancer cells and in human umbilical vein endothelial cells but had no effect on COX-2 expression induced by Escherichia coli lipopolysaccharide in monocytic THP-1 cells. These data suggest that the nuclear export of COX-2 mRNA may be rate-liming in a cell-specific manner. LMB may be useful to control COX-2 expression in various human diseases in which COX-2 plays a pathogenetic role.

publication date

  • December 4, 2002

Research

keywords

  • Cyclooxygenase Inhibitors
  • Fatty Acids, Unsaturated
  • Isoenzymes
  • Karyopherins
  • Prostaglandin-Endoperoxide Synthases
  • Receptors, Cytoplasmic and Nuclear
  • Transcription, Genetic

Identity

Scopus Document Identifier

  • 0037474226

PubMed ID

  • 12468543

Additional Document Info

volume

  • 278

issue

  • 5