Profiling of histone modifications in prostate cancer cells in response to androgen deprivation and the onset of the neuroendocrine phenotype

Androgen deprivation therapy (ADT), also called chemical castration, is one of the prevailing treatments of local and metastatic prostate cancer enabling inhibition of the Androgen Receptor (AR) pathway and tumor regression. However, the response to therapy varies among patients with some showing symptomatic relief and prolonged survival, while others relapsing in less than 5 years or failing to respond (reviewed in Harris et al, 2009). These clinical trajectories are in part due to emergence of mechanisms allowing maintenance of the AR activity, often observed in CRPC tumors, and progressive cell reprograming enabling androgen-independent growth. In some case CRPC tumors progressively evolve in highly agressive AR-negative neuroendocrine prostate cancer (NEPC). In this project we aimed to profile histone modifications associated with actively transcribed and repressed regions in the dynamic in vitro system recapitulating the CRPC and NEPC onset. Hormone-sensitive LNCaP cells were grown in DHT-supplemented medium. In this condition cells exhibit an epithelial-like morphology and actively proliferate under the control of AR. Androgen deprivation results in growth arrest and progressive emergence of the neuroendocrine phenotype characterized by AR signalling inactivation, expression of neuroendocrine genes and change in morphology (Terry et al, 2013).