2-Methoxyestradiol mediated signaling network in pancreatic cancer.

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.

• Authors: Aruna Basu, Subrata Haldar
• Journal: Frontiers in bioscience (Landmark edition) (Front Biosci (Landmark Ed)) Vol. 14 Issue 6 Pg. 2170-80 (01 01 2009) ISSN: 2768-6698 [Electronic] Singapore
• PMID: 19273191 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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