Molecular Mechanisms of Prostate Cancer Progression
Abstract
In studies to define the mechanisms involved in the progression of immortal, non-tumorigenic prostate cells to a tumorigenic state, we have found that molecular chaperones are elevated, which causes increased telomerase activity. In order to determine the importance of the chaperone increase during prostate cancer progression, we have taken a 2-pronged approach, using both genetic and pharmacologic approaches: 1-define whether ectopic chaperone expression results in transformation, and 2-determine whether chaperones are targets for prostate cancer therapy. The hsf-1 transcription factor has been over-expressed in non-tumorigenic prostate cells, resulting in increased hsp90 and hsp70 expression, an upregulation of telomerase, and no effect on tumorigenicity. However, preliminary data suggests that hsf-1 may directly effect telomerase expression, which would further define the regulation of telomerase during cancer progression. Using both a pharmacologic (radicicol, a specific hsp90 inhibitor) and genetic (siRNA to hsp90) approaches, prostate cancer cell lines exhibit only a transient decline in telomerase activity but a significant decrease in telomeres, which we have shown to be directly damaged by free radicals produced as a result of deregulation of the nitric oxide synthase pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA442183
Entities
People
- Lynne W. Elmore
- Shawn E. Holt
Organizations
- Virginia Commonwealth University