Prevention of Development of Recurrent Growth of Prostate Cancer

摘要

The purpose of the proposed studies is to identify and then target one gene or a small number of genes critical for the development of recurrent growth of CaP. Differential expression analysis, subtractive hybridization and immunohistochemistry were used in the androgen-dependent human prostate cancer CWR22 model to identify 10 genes whose expression might be associated with the onset of CaP recurrence. In the first year of the proposed studies, we visually scored 8 gene proteins in CWR22 tumors on day 120 after castration and identified thioreductase-1, tomoregulin and IGFBP-5 as potential targets; developed a hybrid immunostaining protocol for comparison of expression of antigens in proliferating versus non-proliferating cells; collected the necessary reagents (BrdU-labeled tumors); and demonstrated the feasibility of an antisense approach. In year 2, the grant was suspended alter 6 months to allow for transfer to Roswell Park Cancer Institute (RPCI). Quantitative image analysis confirmed that thioreductase-1 expression is higher in proliferating compared to non-proliferating cells in CWR22 tumors that demonstrate growth after castration. Three other nuclear proteins (including Nkx3.1 that was differentially expressed upon visual analysis) revealed no difference using image analysis. Image analysis of seven cytoplasmic proteins is underway using a new image analysis method. In the remaining 1.5 years of the proposed studies, we will complete the image analysis all 10 proteins of interest; examine the genes of interest from the CWR22 model for expression in clinical specimens; and inhibit the expression of the genes of interest using antisense therapy in vitro in CaP cell lines and in vivo in the CWR22 model.