The Role of Androgen Receptors in Androgen Independent Prostate Cancer
Annual summary rept. 1 Jul 1999-30 Jun 2000
BAYLOR COLL OF MEDICINE HOUSTON TX
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Mutations in the AR, changes in growth factor signaling pattern or amplification of the AR may be responsible for androgen independent prostate cancer AIPC. The aim of this project was to look for changes in the AR in the tumors of patients with AIPC. Due to poor preservation of DNA and low frequency of the AR mutations in available samples I studied two different set of samples. Tumors from patients with prostate cancer before and after androgen ablation therapy AA and lymph node metastases from patients who did not receive any AA therapy. In this report I describe the identification of three AR mutants. S863P isolated from lymph node metastases does not bind Rl881 and is transcriptionally inactive regardless of the ligands tested. K580R, another lymph node metastatic, DNA binding domain mutant, shows promoter and cell type specific transcriptional activity. Of the 10 patients analyzed before and after AA therapy, one patient showed an expansion of poly-glutamine repeat from Q20-Q26 following AA therapy. ARQ26 shows reduced transcriptional activity compared to the ARQ20. Future work will include further characterization of the identified tumors and screening of tumors with and without the AR mutations for the AR amplification and activation of MAPK.
- Anatomy and Physiology
- Medicine and Medical Research