Down-Regulation of Proline Rich Homeodomain/Haematopoietically Expressed Homeobox Expression in Prostate Cells Enables Tumour Initiation and Tumour Growth

Background: The Proline Rich Homeodomain/Haematopoietically Expressed Homeobox (PRH/HHEX) transcription factor down-regulates the proliferation of prostate cells, and it has been suggested that this protein acts as a tumour suppressor in prostate epithelial cells. Results: Here, we show that the HHEX gene encoding PRH, located at chromosome 10q23, is often deleted in prostate cancer cells. Moreover, the gene encoding PRH displays increased CpG methylation in prostate cancer cells, and PRH mRNA levels and protein levels are decreased in high Gleason grade prostate tumours. Using a doxycycline-inducible model, we show that over-expression of PRH in prostate cancer cells reduces cell proliferation and cell migration in vitro and inhibits tumour growth and tumour initiation in a mouse xenograft model. Similarly, PRH over-expression in a syngeneic mouse model reduces tumour growth. Interestingly, the inhibition of Protein Kinase CK2 in this model results in increased PRH protein levels in vitro, decreased cell viability, and reduced tumour growth in vivo. Conclusions: PRH acts as a tumour suppressor protein in prostate cancer cells and the re-establishment of PRH activity in these cells through the inhibition of PRH phosphorylation, or through other means, could be a useful approach to prostate cancer treatment.