The Role of ETS Transcriptional Regulation in Hormone Sensitive and Refractory Prostate Cancer

Abstract

Most advanced prostate tumors are dependent upon hormonal regulation of the transcriptional activity of the androgen receptor (AR). Current ASCO recommendations for initial treatment of advanced disease target the hormonal mediated regulation of AR activation through androgen deprivation therapy. Despite early treatment efficacy, most prostate tumors progress and re-activate AR transcriptional regulation through alternative biological mechanisms that allow them to circumvent the requirement for androgen. It is the temporal and spatial recruitment of specific AR transcriptional complexes to the promoters of cancer associated target genes that promotes the tumorigenic phenotype in prostate cancer. Increasing published data associates the E Twenty Six (ETS) family of transcription factors with prostate cancer progression and with the transcriptional activity of the AR. Evidence suggests that ETS factors act in concert to both positively and negatively regulate the pathways that control progression to metastatic cancer in prostate tissues. Given the critical roles both ETS factors and the AR play in the development of prostate cancer, mechanistic insight into their transcriptional co-regulation during the hormone sensitive and hormone refractory phases of progression will be provided by determining the contribution of ETS, AR and ETS-AR mediated regulatory control. This review examines the current depth of understanding of the role of the ETS family of transcription factors as transcriptional elements that confer the carcinogenic response to aberrant hormonal activity during prostate cancer progression.