Molecular Mechanisms of Estrogen and Antiestrogen Resistance
Abstract
This is an Academic (Career Development) Award. Consistent with this award, the PI continues to ".. appraise critically the state of the science in a particular aspect of breast cancer research and to forge new avenues of investigation." In this application, the studies are focused on antiestrogen resistance. With respect to the career development aspects, several original studies and reviews relevant to this application have been published, others have been submitted for publication. We continue to apply state-of-the-art technologies to addressing resistance, including the development of novel approaches to data mining and analysis. The studies of interferon regulatory factor-1 (IRF-l) continue. We have now completed the initial studies of the IRF-l transfected cells and have developed and begun to test a dominant negative IRF-1 construct. Immunohistologic methods for correlative studies on human breast tissues are being developed and we hope soon to study the expression of nucleophosmin, NFkappaB, IkF-1 and X-box binding protein -l (hxBP-l) and any correlations with known prognostic markers. We also have explored the effects of in utero Tamoxifen exposure on mammary gland development and subsequent susceptibility to chemical carcinogenesis. The role of the steroid sulfatase in affecting estrogen dependence in vitro and in vivo also was explored. Data show that overexpression of this enzyme can release sufficient intracellular estrogens to support estrogen-dependent growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA403335
Entities
People
- Robert R. Clarke
Organizations
- Georgetown University