Open Access
Article
2-Methoxyestradiol mediated signaling network in pancreatic cancer
Aruna Basu1,Subrata Haldar1
1
Center for Biomedical Sciences, Department of Pharmacology, Case Comprehensive Cancer Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109, USA. abasu@metrohealth.org
DOI: 10.2741/3369 Volume 14 Issue 6, pp.2170-2180
Published: 01 January 2009
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.

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Aruna Basu, Subrata Haldar. 2-Methoxyestradiol mediated signaling network in pancreatic cancer. Frontiers in Bioscience-Landmark. 2009. 14(6); 2170-2180.