Apoptosis and Tumor Progressionin Prostate Cancer
Annual rept. 1 Feb 2004-31 Jan 2005
NOTRE DAME UNIV IN
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In the period covered by this application we have repeated a large scale animal study to investigate the effect of chronic exposure of PC-346CRFP which expresses the wild type receptor to Casodex. The intermediate criteria we are monitoring are primary tumor volume, rates of proliferation as measured by BrdU incorporation and apoptosis as measured by TUNEL staining. We have standardized an efficient methodologies for isolating cells from primary tumors expressing REP by fluorescence activated cell sorting FACS and by laser capture micro-dissection LCM . We have intitiated a comprehensive micro-array based bioinformatics effort to identify genes whose expression is modulated by Casodex to characterize the molecular events underlying metastatic progression of PC-346CRFP cell. The changes in gene expression detected by micro-array are being validated by QT-PCR using SYBR green. The results of these experiments are also being compared to the effects of Casodex in LNCaP cells which has a mutated androgen receptor, and to the changes in gene expression seen in the PC-346CRFP primary tumors and metastases from animals chronically treated with Casodex. These studies will identify changes in cell behavior and gene expression that lead to the acquisition of an invasive phenotype.
- Anatomy and Physiology
- Medicine and Medical Research