Mechanism of AR transactivation in CRPC cells: role of Nrf2, p65-Nrf1 and p120-Nrf1.

In CRPC cells (e.g. C4-2B), despite ADT, residual androgens (e.g. DHT) increase nuclear p65-Nrf1 and simultaneously decrease both total Nrf2 and nuclear p120-Nrf1 levels. Nuclear p65-Nrf1 associates with nuclear AR and with the AR transcription complex bound to the ARE sequences in promoter/enhancer regions of genes that regulate prostate tumor growth. Therefore, CRPC cells may utilize the AR coactivator p65-Nrf1 to enhance AR transactivation and facilitate the recurrence of PCa.