High Throughput Screen to Identify Novel Drugs that Inhibit Prostate Cancer Metastasis

摘要

We have proposed to developed indicator cell lines that would allow for the high throughput screening (HTS) for compounds that potentially inhibit prostate cancer (CaP) metastasis. The cell lines are based on stably expressing a construct containing the promoter of SSeCKS/ gravin/AKAP12- a metastasis- suppressor gene downregulated in CaP progression- linked to a green fluorescence protein (GFP), plus a control reporter, in metastatic CaP cells, and then screening for compounds that induce GFP. We also proposed to characterize the pathways controlling SSeCKS expression in CaP progression. UPDATE: Our data indicate that SSeCKS re-expression can be induced in CaP cell lines using inhibitors of histone deacetylation (TSA) but not by inhibitors of methylation (5-aza-C). We have now produced stable indicator C4-2 cells with GFP expression inducible by TSA and by retinoids. We have also characterized the cis- and trans-acting factors of the human SSeCKS promoter required for transcriptional suppression in CaP cells.