The ETS family member GABPa mediates the development of castrate-resistant prostate cancer (BeadChip)

In prostate cancer, the androgen receptor (AR) is a key transcription factor at all disease stages. We recently showed that during progression to castrate-resistant prostate cancer the AR acquires the ability to bind to a distinct set of genomic sites in tissue samples and that some of the genes that are regulated by the AR in these conditions correlate with poor prognosis. Based on this work we hypothesised that the AR is reprogrammed through interactions with other transcription factors. In the present study we show that GABPá, an ETS transcription factor which is upregulated in CRPC, is an AR-interacting transcription factor. Ectopic expression of GABPA in prostate cancer cell-lines enables them to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. Cells were made to either overexpress GABPa or have it knocked down; these conditions also had empty vector and non-targetting controls respectively. All four treatments were carried out with and without androgen for the LNCaP and c42b cell lines. Biological and technical replicates were used.