title: The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer?
abstract: The retinoblastoma tumor suppressor gene (RB1; encoding RB) is often cited as a gatekeeper, whose inactivation - direct or indirect - is a rate-limiting step for tumor initiation. However, in this issue of the JCI, Sharma et al. show that RB1 loss is a late event in human prostate cancer that is coincident with the emergence of castrate-resistant metastatic disease. This role for RB1 was linked to both E2F transcription factor 1-driven upregulation of the androgen receptor (AR) and increased recruitment of the AR to target gene promoters. This unexpected function for RB1 in late-stage cancer calls upon us to reassess the significance of RB1 inactivation in other cancers in terms of its timing, function in disease etiology, and relevance for cancer therapy.
authors.affiliation: Ben May Department for Cancer Research, Gordon Center for Integrative Sciences, University of Chicago, Chicago, Illinois, USA. kmacleod@uchicago.edu
authors.forename: Kay F
authors.initials: KF
authors.lastname: Macleod
mesh_terms: D050687:E2F1 Transcription Factor / Q000502:physiology; D016161:Genes, Retinoblastoma; D006801:Humans; D008297:Male; D008954:Models, Biological; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D011944:Receptors, Androgen / Q000502:physiology; D016160:Retinoblastoma Protein / Q000502:physiology
chemical_list: C410798:AR protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011944:Receptors, Androgen; D016160:Retinoblastoma Protein