Abstract 4370: GSK3{alpha}/{beta} inhibition as a drug target in prostate cancer

Despite what its namesake suggests, Glycogen Synthase Kinase 3 (GSK3) is a kinase that is implicated in a myriad of signalling pathways and has recently received considerable interest due to its conflicting roles oncogenesis. Though GSK3 has classically been regarded as a tumour suppressor due to in role in supressing WNT signalling, emerging evidence suggests that GSK3 also functions as a tumor promoter by facilitating tumor cell survival and conferring drug resistance in cancer. These tumor promoting effects have been partly linked to the expression of certain NFκB target genes, whose expression in some cancers are influenced by direct GSK3 phosphorylation of NFκB's p65 subunit. Given the complex interplay between GSK3 and the androgen receptor in prostate cancer (PCa), and the inverse correlation between the androgen receptor status and NFκB, we investigate the potential of GSK3 inhibitors to treat and overcome drug resistance in PCa.A kinase inhibitor screen for 80 compounds and additional chemical inhibitors for GSK3 was carried out using the JANUS Automated Workstation at the robotics facility at NUI Galway, Ireland. The cellular fractions for treated cells were separated and assessed for differences in expression between the cytoplasmic and nuclear compartments using western blotting. Flow cytometry and western blotting using antibodies for markers of apoptosis were used to assess for mode of cell death. Differences in gene expression of NFκB target genes were asse...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research