High Throughput Screen to Identify Novel Drugs that Inhibit Prostate Cancer Metastasis
Annual rept. 20 Sep 2004-19 Sep 2005
ROSWELL PARK CANCER INST BUFFALO NY
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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 gravinAKAP12- 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. 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 and DU145 cells, the latter of which is more inducible by TSA. We have also characterized the cis- and trans-acting elements of the human SSeCKS promoter required for transcriptional suppression in CaP cells.
- Medicine and Medical Research