Reducing prohibitin increases histone acetylation, and promotes androgen independence in prostate tumours by increasing androgen receptor activation by adrenal androgens.

ABSTRACT: Prostate cancers (PCs), initially responsive to anti-androgen therapies, often advance to a hormone-refractory 'castrate-resistant' PC (CRPC) stage. However, the androgen receptor (AR) pathway remains active and key for cell growth and gene expression within tumours, even in the apparent absence of hormone. Proposed mechanisms to explain progression, including AR amplification/mutation, are insufficient to completely explain CRPC and possible roles of AR cofactors such as prohibitin (PHB) are poorly understood. We investigated whether PHB loss could sensitise PC cells and tumours to adrenal gland-derived androgens, which persist even after androgen ablation, hence contribute to development of CRPC. Using a pair of PC cell lines, inducibly expressing ectopic cDNA or RNAi for PHB, responses

SUBMITTER: Dart DA 

PROVIDER: S-EPMC3427022 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature