Oxidative stress and androgen receptor expression in castration-resistant prostate cancer

Masaki Shiota, Akira Yokomizo, Yasuhiro Tada, Junichi Inokuchi, Seiji Naito

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

There are few successful therapies for castration-resistant prostate cancer (CRPC). Recently, CRPC has been thought to result from augmentation of the androgen/androgen receptor (AR)-signaling pathway, with AR overexpression having been observed in most cases. In a previous study, we found that Twistl, a member of the basic helix-loop-helix transcription factors, regulated AR expression via binding to E-boxes within the AR promoter region. Twistl. which is known to be a stress-inducible factor, as well as AR, was upregulated in response to hydrogen peroxide. Furthermore, castration-resistant LNCaP derivatives and hydrogen peroxide-resistant LNCaP derivatives expressed high levels of both Twistl and AR, and they exhibited a castration-resistant phenotype, which was reversed by AR knockdown. Blockade of androgen/AR signaling by androgen deprivation and AR knockdown increased intracellular reactive oxygen species. Silencing of Twistl suppressed the cell growth of the LNCaP cells as well as the castration-resistant LNCaP derivatives by inducing cell-cycle arrest at the Gl phase and cellular apoptosis. These findings indicate that oxidative stress induced by castration may promote AR overexpression through Twistl overexpression, which could result in a gain of castration resistance. Modulation of castration-induced oxidative stress or Twistl/AR signaling may be a promising strategy for developing novel therapeutics in prostate cancer, even in cases of CRPC. Further intensive research in this field is essential in order to improve the outcome of therapy for advanced prostate cancer.

Original languageEnglish
Pages (from-to)97-102
Number of pages6
JournalNishinihon Journal of Urology
Volume72
Issue number3
Publication statusPublished - Mar 2010

All Science Journal Classification (ASJC) codes

  • Urology

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