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

Autor: Terry, S., Ploussard, G., Allory, Y., Nicolaiew, N., Boissière-Michot, F., Maillé, P., Kheuang, L., Coppolani, E., Ali, A., Bibeau, F., Culine, S., Buttyan, R., de la Taille, A., Vacherot, F., Boissière-Michot, F, Maillé, P
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Zdroj: British Journal of Cancer; 9/8/2009, Vol. 101 Issue 6, p951-956, 6p, 1 Color Photograph, 1 Chart, 2 Graphs
Abstrakt: Background: Class III beta-tubulin (betaIII-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 betaIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, betaIII-tubulin expression remains largely uncharacterised in prostate cancer.Methods: In this report, we evaluated the expression of betaIII-tubulin in 138 different human prostate tumour specimens by immunohistochemistry from patients with hormone-treated or hormone-untreated prostate cancer. betaIII-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 betaIII-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 betaIII-tubulin. These findings were supported by in vitro and in vivo settings.Conclusion: Our data indicate that betaIII-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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index