ER/AP-1 Modifications in Tamoxifen-Resistant Human Breast Tumors
Abstract
Endocrine therapy in the form of aromatase inhibitors or antiestrogens like tamoxifen is the treatment of choice for most patients with estrogen receptor (ER)-positive breast cancers. However, it remains unclear why up 30-50% of ER-positive tumors demonstrate clinical resistance to these forms of ER-targeted treatments. It is known that ER that is structurally altered such that it cannot bind directly to its ERE, can still affect gene expression via protein-protein interactions with other transcription factors (e.g. AP-1, Sp1, NF-kappaBeta, etc.); these protein-protein interactions are mediated by ER domains other than the ER-DBD. The goat of the current study is to identify the molecular changes induced by oxidant stress that result in altered intracellular ER structure, account for its loss of function (DNA-binding), and thereby produce a clinically more aggressive form of tumor behavior that includes loss of responsiveness to ER- targeted endocrine therapy. In order to accurately study these oxidative effects I have been developing a double alkylation, double digestion protocol. The protocol has evolved from its original version (described last year) due to unexpected pitfalls. The revised protocol and its application to the study of oxidant stressed ER isolated from cell lines and tumor samples are described in this report.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADB285876
Entities
People
- Christopher C. Benz
- Jose E. Meza
Organizations
- University of California, San Francisco