Accession Number:

ADB281622

Title:

AP-1 Activity in Tamoxifen-Resistant Human Breast Tumors

Descriptive Note:

Annual rept. 1 Sep 2000-31 Aug 2001

Corporate Author:

CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s):

Report Date:

2001-09-01

Pagination or Media Count:

14.0

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 ERAP-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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE