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Role of the Neddylation Enzyme Uba3, A New Estrogen Receptor Corepressor, in Breast Cancer

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Final rept. 1 May 2002-30 Apr 2005

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Estrogens play important roles in both the onset and malignant progression of breast cancer. The content of estrogen receptors in breast tumors is a valuable predictor of whether a patient will respond to therapy with antiestrogens, such as tamoxifen and fulvestrant ICI 182,780. Expression and activity of ER can be lost or impaired in antiestrogen-resistant breast cancer. The proposed studies are designed to test the overall hypothesis that the ubiquitin-like NEDD8 protein modification pathway represses estrogen action by facilitating degradation of ER protein. Perturbation of this pathway may prove instrumental in breast tumor progression alternatively, activation of this pathway may prove to be a valid target for novel therapeutics. This study on mechanisms that regulate ER levels and activity are highly relevant to the development and progression breast cancer, including tumor progression to states of hormone independence and antiestrogen resistance. Thus, understanding how the estrogen receptor is regulated is an area of research critical to understanding the tissue selective pharmacology of estrogens. In addition, tamoxifen and other selective estrogen receptor modulators target the estrogen receptor, and this study is of the utmost relevance to those important therapies.

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  • Biochemistry
  • Medicine and Medical Research

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