Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification
Abstract
Initially prostate cancer development is driven by the male hormone androgen through the androgen receptor, however, in some patients androgen receptor becomes dysfunctional at late stages of tumorigenesis. Early knowledge of the androgen receptor dysfunctions, what would make prostate tumors refractory to routine androgen ablation therapy, should help in patient stratification for other emerging therapeutic strategies. We proposed a novel approach for evaluating potential dysfunctions of the androgen receptor by measuring the expression of a functionally relevant panel o f genes. This approach is direct and can be easily addressed from human prostate cancer tissues (surgery or diagnostic biopsy specimens) at early stages of the disease. Within the first reporting period we have designed, tested and completed the quality control of specific proves and primers evaluating the androgen dose and time kinetics of endogenously expressed PSA/KLK3. PMEPA1, NKX3.1, ODC11, AMD1 and TMPRSS2-ERG genes in VCaP cell culture model. Preliminary evaluation of an initial number of whole-mounted sections of RP specimens with prostate cancer by the Immunohistochemical assessment of AR, ERG , NKX3.1, and PSA proteins indicated reduced expression of ARP genes in a subset of th4e cases. The proposed research we will provide a quantitative index of AR dysfunction for enhancing disease prognostic characteristics to improve accuracy and to stratify patients for specific therapeutic approaches at early stages of prostate cancer treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA570064
Entities
People
- Albert Dobi
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine