Molecular Mechanisms of Prostate Cancer Progression
Abstract
In studios 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 along with telomerase activity. Elevated chaperone function results in an increase in telomerase assembly and is associated with prostate cancer progression. In order to determine the importance of the chaperone increase, we are investigating, both genetically and pharmacologically, whether ectopic chaperone expression results in transformation and 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 and an upregulation of telomerase. Preliminary data suggests that exogenous hsf-1 has little effect on tumorigenic growth. Using both a pharmacologic (radicicol, a specific hsp90 inhibitor) and genetic (siRNA to hsp90) approaches, malignant prostate cancer cell lines show only a transient decline in telomerase activity but a significant decrease in telomere length, suggesting that chaperones function at the telomere independent of their interaction with telomerase.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423208
Entities
People
- Shawn E. Holt
Organizations
- Virginia Commonwealth University