Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer progression [array]

Whether the nuclear fraction of mTOR plays a role in prostate cancer (PCa) and can participate in direct transcriptional crosstalk with the androgen receptor (AR) is as yet unknown. The intersection of gene expression, DNA binding-events, and metabolic studies uncovered the existence of a nuclear mTOR-AR transcriptional axis dictating the metabolic rewiring and nutrient usage of PCa cells. In human clinical specimens, nuclear localization of mTOR was significantly associated with metastasis and castration-resistant PCa (CRPC), correlating with a sustained metabolic gene program governed by mTOR in that context. This study thus uncovers an unexpected function of mTOR and underscores a paradigm shift from AR to mTOR as being the master transcriptional regulator of cell metabolism during PCa progression. We used microarrays to investigate the role of nuclear mTOR in prostate cancer cell transcriptional regulation by androgens in LNCaP cells. Cells were seeded in media deprived from steroids. 48h later, cell were treated with 10nM R1881, 100nM torin 1 (an mTOR inhibitor), or vehicles (EtOH, DMSO) for 48h. Triplicate samples were sent for each conditions.