AP-1 Activity in Tamoxifen-Resistant Human Breast Tumors
Abstract
Tamoxifen is the hormonal therapy of choice for patients whose tumors are classified estrogen receptor (ER)- positive. However, in advanced breast cancer, ER-positive tumors that may be initially responsive to tamoxifen become resistant. ER can interact with the activator protein-i (AP-1) transcription factor complex through protein-protein interactions and tamoxifen functions as an agonist in coactivating ER/AP-1 in some ER positive cells. Tamoxifen has been shown to induce oxidative stress and tamoxifen resistant ER positive cell lines are associated with increased AP-1 binding, suggesting that enhanced AP-1 activity can account for tamoxifen- stimulated growth. in this study, I focus on the functional effect of oxidant stress on the zinc finger structure of ER. In order to accurately study the effect of the oxidant stress on full-length recombinant ER and on ER purified from cell lines and tumor samples, I have developed an alkylation and in gel-digestion protocol. This procedure is described in detail and will allow me to circumvent the unexpected pitfalls discussed in this report. Additionally, an analysis of 70 ER-positive breast tumors extracts for AP-1 and Sp1 DNA- binding and phosphorylated extracellular signal-regulated protein kinase 5 (P-Erk5) content has been completed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADB281622
Entities
People
- Jose E. Meza
Organizations
- University of California, San Francisco