Increased expression of class III β-tubulin in castration-resistant human prostate cancer

BACKGROUND: Class III beta-tubulin (beta III-tubulin) is expressed in tissues of neuronal lineage and also in several human malignancies, including non-small-cell lung carcinoma, breast and ovarian cancer. Overexpression of beta III-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, beta III-tubulin expression remains largely uncharacterised in prostate cancer. METHODS: In this report, we evaluated the expression of beta III-tubulin in 138 different human prostate tumour specimens by immunohistochemistry from patients with hormone-treated or hormone-untreated prostate cancer. beta III-tubulin expression was also examined in various prostatic cancer cell lines including in androgen-sensitive human prostate cancer cells, LNCaP, grown in androgen-depleted medium in 2D cultures or as tumour xenografts when the host mouse was castrated. RESULTS: Whereas moderate-to-strong beta III-tubulin expression was detected in only 3 out of 74 (4%) hormone-naive tumour specimens obtained from patients who never received hormone therapy, 6 out of 24 tumour specimens (25%) from patients treated for 3 months with neoadjuvant hormone therapy and 24 out of 40 (60%) castration-resistant tumour specimens from chronic hormone-treated patients were found to express significant levels of bIII-tubulin. These findings were supported by in vitro and in vivo settings. CONCLUSION: Our data indicate that beta III-tubulin expression is augmented in prostate cancer by androgen ablation and that the expression of this beta-tubulin isoform is associated with the progression of prostate cancer to the castration-resistant state, a stage largely responsible for mortality from prostate cancer. British Journal of Cancer (2009) 101, 951-956. doi:10.1038/sj.bjc.6605245 www.bjcancer.com Published online 18 August 2009 (C) 2009 Cancer Research UK