Although it has been well known that oxidative stress promotes prostate carcinogenesis, the role of oxidative stress in the progression of prostate cancer, especially in castration-resistant progression, has remained obscure. Accordingly, we attempted to elucidate its mechanism and apply our findings to the clinical setting. To date we have been able to show that; (i) androgen-deprivation therapy induces oxidative stress in prostate cancer, and (ii) oxidative stress up-regulates the oncogenic transcription factors, Twistl and Y-box-binding protein-1 (YB-1), resulting in androgen receptor (AR) induction as well as activated AR signaling through the AR cofactor and intracellular signaling pathway, which contribute to castration-resistant progression. As regards application to the clinical setting, we have revealed promising results of antioxidant therapy as well as Twistl and YB-l-targeting therapies against prostate cancer combined with androgen-deprivation therapy. In conclusion, our results suggest that castration-resistant prostate cancer may be derived from pathways that activate invasion and metastasis by Twistl and resist cell death by YB-1, which can be reversed through the inhibition of these pathways.
|Number of pages||6|
|Journal||Nishinihon Journal of Urology|
|Publication status||Published - Apr 2013|
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