In prostate cancer cells, de-repression of HES5 with the demethylating agent 5-aza-2′-deoxycytidine resulted in a delayed downregulation of HES6 (Fig. 3c), consistent with HES5 repression of HES6. We also observed an inverse relationship between HES5 and HES6 expression in a series of primary tumours compared with benign prostate samples, where HES5 expression decreased and HES6 expression increased in tumour vs benign prostate samples (Fig. 3d and e). Here, HES5 is linked to Familial prostate cancer.