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

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.