WFDC1/ps20 expression is frequently downregulated or lost in prostate cancer (PCa) and ps20 has demonstrated growth-suppressive functions in numerous tumour model systems, although the mechanisms of this phenomenon are not understood.
Gene expression microarray analysis and further expression validation suggests that the Dickkopf-1 (Dkk1) gene is up-regulated in WFDC1 over-expressing cell lines, suggesting that the tumor suppressive function of WFDC1 may be partially a result of up-regulated Dkk1 gene expression, which is known to be a potent inhibitor of the Wnt signaling pathway.
We, therefore, propose that WFDC1/ps20 may not be a classical tumor suppressor gene, but might play a role in the maintenance of the normal extra cellular matrix milieu in the prostate.
To address the potential effects of ps20 in a tumor microenvironment, we used the DRS model to evaluate both angiogenesis and tumorigenesis of tumors generated under either ps20 or control conditions.
We further investigated the role of WFDC1 as a tumour suppressor gene candidate in five hepatocellular cell lines and in tumours exhibiting LOH by means of mutation, promoter methylation and gene expression analysis.