2-Methoxyestradiol mediated signaling network in pancreatic cancer

Front Biosci (Landmark Ed). 2009 Jan 1;14:2170-80. doi: 10.2741/3369.

Abstract

2-Methoxyestradiol (2-ME), an endogenous metabolite of 17 beta-estradiol, is known to be a potent inhibitor of neovascularization. Our previous studies have shown that 2-ME can suppress growth of pancreatic tumor cells in vitro and in vivo by the induction of apoptosis (Cancer Res 66: 4309-18, 2006). In order to better comprehend the signaling modulators of 2-ME in pancreatic cancer, we employed a PowerBlot Western Array screening system. Our proteomic profiling has provided framework to define the novel mechanisms of actions of 2-ME in pancreatic cancer. Interestingly, this high-throughput analysis identified proteins such as Rac1, Gelsolin, Glucocorticoid receptor (GR), Smad 2/3, Smad 4, IRS-1, which were not previously reported with 2-ME response. Interestingly, 2-ME modulated down regulation of GR level is accompanied by NF-k B activation in 2-ME responsive but not in resistant pancreatic cancer cells. In view of this observation, possible reciprocal relationship between GR and NF-kappaB activation might be an important regulatory factor in 2-ME mediated demise of a subpopulation of pancreatic cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • Apoptosis
  • Blotting, Western
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism
  • NF-kappa B / metabolism
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Receptors, Glucocorticoid / metabolism
  • Signal Transduction / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cell Cycle Proteins
  • Hypoxia-Inducible Factor 1
  • NF-kappa B
  • Receptors, Glucocorticoid
  • Vascular Endothelial Growth Factor A
  • Estradiol
  • 2-Methoxyestradiol