Molecular Mechanisms of Metastatic Progression in Breast Cancer
Abstract
Clusterin is a multifunctional glycoproptein involved in tissue remodeling and apoptosis. However, recent studies have demonstrated that clusterin expression correlates with tumor grade in prostate cancer and in one retrospective study has been associated with tumor progression in breast cancer. Furthermore clusterin expression has been correlated with resistance to cytotoxic compounds such as TNF-alpha in prostate cancer, suggesting that clusterin may play a role in surviving cells. In our studies, we have focused on determining whether clusterin plays a causative role in the progression of human breast cancer by promoting cell survival, increasing cell motility and resistance to cytotoxic drugs. Our studies have utilized an ER-alpha positive non-invasive MCF-7 cell line, an MCF-7 cell line genetically engineered to overexpress clusterin(MCF-7CLU) and an ER-alpha negative breast negative invasive SUM-159PT cell line. Our major finding to date are that MCF-7CLU cells express 5-10 fold higher levels of intra- and extra-cellular clusterin as compared to parental MCF-7 cells. The MCF-7CLU cell line exhibits increased growth rates, altered cellular morphology, a dramatic increase (10-fold) in invasive potential and a delayed apoptotic response to cytotoxic compounds such as TNF-alpha and Tamoxifen in comparison to the parental MCF-7 cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA434588
Entities
People
- Louise A. Flanagan
Organizations
- University of Notre Dame