Role of the Neddylation Enzyme Uba3, a New Estrogen Receptor Corepressor, in Breast Cancer
Abstract
Estrogen are well known to play an important role 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 ubiguitin-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. Receptor coregulators, such as Uba3, may represent a crucial point of control of estrogen action. Thus, understanding how coregulators influence the estrogen receptor is an area of research critical to understanding the tissue selective pharmacology of estorgens, tamoxifen and other SERMS and of the utmost relevance to therapies that target ER and other nuclear receptors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA420492
Entities
People
- Kenneth P Nephew
Organizations
- Indiana University