X-Box Binding Protein-1 in Breast Cancer
Abstract
The factors driving resistance to antiestrogens are unknown. Comparing the transcriptomes of antiestrogen responsive and resistant MCF-7 variants by serial analysis of gene expression, we have implicated several genes, including the human X-box binding protein-1 (XBP-1). XBP-1 is a cAMP response element (CRE) binding protein associated with estrogen receptor (ER) expression in gene expression profiles of human breast cancers. We hypothesize that overexpression of XBP-1 and/or activation of CRE contribute functionally to the ability of responsive cells to survive the metabolic stresses induced by exposure to antiestrogens. We also hypothesize that measuring expression of the XBP-1 protein will assist in better identifying antiestrogen resistant and/or responsive tumors. Aim 1: We will further study the likely functional role of XBP-l/CRE by overexpression through transfection into responsive cells, and inhibiting expression in resistant cells using novel CRE oligonucleotide decoys, antisense and/or ribozymes. Effects of these molecular manipulations on responsiveness to antiestrogens will be studied in vitro and in vivo. Aim 2: We will explore the prognostic and predictive significance of XBP-1 expression in a unique series of human breast cancer biopsies. Thus, we will assess the extent to which XBP-1 is an independent prognostic factor, and whether it is associated with response to antiestrogens. Where possible, we will explore whether XBP-1 expression data allow us to build better predictive/prognostic models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA433869
Entities
People
- Robert R. Clarke
Organizations
- Georgetown University