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

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

研究成果: ジャーナルへの寄稿学術誌査読

2 被引用数 (Scopus)


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.

ジャーナルNishinihon Journal of Urology
出版ステータス出版済み - 3月 2010

!!!All Science Journal Classification (ASJC) codes

  • 泌尿器学


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