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


CONCLUSIONS
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.
Terry
S
S
INSERM, Unité 955, Créteil F-94000, France. stephane.terry@inserm.fr
Ploussard
G
G
Allory
Y
Y
Nicolaiew
N
N
Boissière-Michot
F
F
Maillé
P
P
Kheuang
L
L
Coppolani
E
E
Ali
A
A
Bibeau
F
F
Culine
S
S
Buttyan
R
R
de la Taille
A
A
Vacherot
F
F
D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000628:therapy; D014404:Tubulin / Q000032:analysis*
C498585:TUBB3 protein, human; D014404:Tubulin
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