A Systems Biology Understanding of Estrogen Receptor Action

Type of Award: Catalyst
Date Awarded: January 2010
Award End Date: December 2011
Amount Awarded: $ 200,000.00
PI(s): Serdar Bulun, MD, Northwestern University; Jonna Frasor, PhD, University of Illinois at Chicago; Yang Dai, PhD, University of Illinois at Chicago;

Abstract: Women are administered hormones, including selective estrogen receptor modulators (SERMs), which target the estrogen receptor (ER), for a variety of reasons, including preventing growth of hormone-dependent breast tumors, improving bone mineral density, or reducing menopausal symptoms. However, these agents often cause detrimental side-effects in other tissues. One such SERM is tamoxifen. Millions of women have taken tamoxifen to block growth of their ER positive breast tumors. However, this same agent can increase proliferation in the uterus, and in turn increase the risk of uterine cancer. Our goal is to use a combination of novel and complimentary approaches to understand why these drugs have different effects in different tissues. Specifically, we will look at the proteins that interact with ER and the genes that change in response to hormone treatment using a completely unbiased approach. We will create regulatory networks of information based on genome-wide, large scale biological data sets that are generated by us and that we collect from publicly available sources. This proposal is to seek support for an innovative research strategy that requires collaboration among investigators at UIC and NU with complementary expertise in bioinformatics, reproductive endocrinology, and molecular mechanisms of ER action. Because of the diverse approaches to be used in this project, none of the investigators could accomplish this work on their own. We hypothesize that integration of proteomic and genomic data through novel bioinformatics approaches will allow us to identify key mechanisms controlling ER activity in different tissues responses to different ligands, such as estrogen and tamoxifen. This, in turn, may lead to novel therapeutic approaches to target the ER in the treatment of hormone-dependent diseases.