The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells
1
Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA
2
Department of Urology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Cancers 2010, 2(2), 1354-1378; https://doi.org/10.3390/cancers2021354
Received: 7 June 2010 / Revised: 18 June 2010 / Accepted: 21 June 2010 / Published: 21 June 2010
(This article belongs to the Special Issue Oxidative Stress and Cancer)
Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in modulating AR expression and signaling in aggressive prostate cancer (PCa) cells. In androgen independent (AI) C4-2B cells, in comparison to the parental androgen dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1 correlated with enhanced AR transactivation. Our findings implicate a crucial balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells. Here we will discuss how understanding the mechanisms by which oxidative stress may affect AR signaling may aid in developing novel therapies for AI-PCa.
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Keywords:
Nrf1 (NF-E2 related factor-1); Nrf2 (NF-E2 related factor-2); prostate cancer; oxidative stress; androgen independence; androgen deprivation therapy; reactive oxygen species (ROS); androgen receptor (AR); di-hydrotestosterone (DHT)
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This is an open access article distributed under the Creative Commons Attribution License
MDPI and ACS Style
Schultz, M.A.; Abdel-Mageed, A.B.; Mondal, D. The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells. Cancers 2010, 2, 1354-1378.
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