Molecular Determinants of Radio Resistance in Prostate Cancer
Abstract
We are studying the radiation response of prostate tissues in relation to the sensing and repair of DNA breaks. Specific aims relate to determining the expression and interaction of DNA repair proteins in vitro using immunoflorescent confocal microscopy and biochemical DNA rejoining assays under both hypoxic and oxic conditions. An in vivo program of prostate xenograft radioresponse and patient biopsy studies will determine the level of DNA repair in situ using immunohistochemistry and immunoflorescent markers. Our studies show that DNA repair protein expression is abnormal in malignant versus normal prostate epithelial cultures, and that particularly the Rad51 protein is defective in localizing to the nucleus following DNA damage. We have accrued 13 patients onto a pre-operative radiotherapy trial and post-irradiation immunohistochemistry supports an induction of p53-pathway signaling following 25Gy in 5 fractions. Future experiments will be designed to determine whether DNA protein focal interactions using 2-photon microscopy can predict the radioresponse of prostate xenografts and human tumors, in vivo. Our studies support the use of novel molecular based therapies that target DNA repair for prostate cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA446687
Entities
People
- Jeremy Squire
- Lathar Lilge
- Michael Milosevic
- Padraig Warde
- Robert G. Bristow
Organizations
- University Health Network