Investigating the Role of Nuclear Clusterin (nCLU) in Lethality and Genomic Instability in Paclitaxel (Taxol) - Treated Human Breast Cancer Cells
Abstract
Clusterin is a protein that has been implicated in many normal physiological processes (tissue remodeling, sperm maturation) as well as many pathological processes (Alzheimer disease, atherosclerosis, cancer) . Our laboratory became interested in clusterin when we identified it as an x-ray induced protein/transcript in human melanoma cells. Recently, we have identified two forms of this protein that are derived by alternative splicing of a single message. The secretory form of clusterin (sCLU) has been shown to have cytoprotective effects after cellular stress and injury. In contrast, a nuclear form of clusterin (nCLU) appears to be cytotoxic. Recently, Redondo et. al demonstrated that sCLU was overexpressed in breast cancer. sCLU over expression may provide a selective advantage in malignant cells. The most effective therapies for breast cancer after surgery include chemo- and radiation therapies. These therapies often fail as the tumor develop drug and radiation resistance. Our lab has shown that sCLU is induced by physiological doses of taxol, taxotere and radiation. Understanding the cellular and molecular responses of malignant and normal cells to these chemo- and radiation therapy would allow us to increase the efficacy of these treatments. Insight into the regulation of sCLU will allow us to better understand some of these processes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA406785
Entities
People
- David A. Boothman
- Tracy Criswell
Organizations
- Case Western Reserve University