Regulation of the Response to Radiotherapy and Hyperthermia in Prostate Cancer by the 26s Proteasome
Abstract
The goal of the proposal was to investigate the novel hypothesis that the proteasome functions as a sensor for hyperthermia and/or irradiation and its response is important in determining the outcome of prostate cancer treatment. In an attached review ((1); Appendix), we discuss the recent evidence indicating critical roles for the 26s proteasome in selectively regulating many vital cell processes, including cell cycle progression, oxidative stress, DNA repair, and cell death. We also show that this system is frequently dysregulated in cancer, including prostate cancer. This proposal is novel in that the roles of the proteasome in the biology and therapy of cancer have been the subject of very few investigations and there are almost no reports on how their activities might influence the response of prostate cancer to therapeutic intervention. We postulated that proteasome activity would vary between prostate cancer cell lines, that hyperthennia and/or radiation would influence proteasome activity, and that this would influence the expression of cell death/survival molecules following treatment in a manner that could determine therapeutic outcome. We further suggested that the 26s proteasome might represent a novel potential target for prostate cancer thernnv one that is as vet. unexnlored.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADA406463
Entities
People
- William H. Mcbride
Organizations
- University of California, Los Angeles