Increased expression of class III beta-tubulin in castration-resistant human prostate cancer.
Increased expression of class III beta-tubulin in castration-resistant human prostate cancer.
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DOI：
10.1038/sj.bjc.6605245
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发表时间：
2009-09-15
影响因子：
8.8
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中科院分区：
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III类β-微管蛋白（β III-微管蛋白）在神经元谱系的组织中表达，也在几种人类恶性肿瘤中表达，包括非小细胞肺癌、乳腺癌和卵巢癌。β III-微管蛋白在这些肿瘤中的过度表达与不利的结局和对紫杉烷类药物治疗的耐药性相关。目前，β III-微管蛋白的表达在前列腺癌中仍然很大程度上未被表征。在这份报告中，我们通过免疫组织化学方法评估了138例不同的人前列腺肿瘤标本中β III-微管蛋白的表达，这些标本来自接受过前列腺切除术或未接受前列腺切除术的前列腺癌患者。还在各种前列腺癌细胞系中检查了β III-微管蛋白表达，包括在2D培养物中在雄激素耗尽培养基中生长的雄激素敏感性人前列腺癌细胞LNCaP中，或在宿主小鼠去势时作为肿瘤异种移植物。而从从未接受过激素治疗的患者中获得的74份未经激素治疗的肿瘤标本中，仅3份（4%）检测到中度至重度β III-微管蛋白表达，接受新辅助激素治疗3个月的患者的24份肿瘤标本中有6份（25%）和接受慢性激素治疗的40份去势抵抗性肿瘤标本中有24份（60%）发现治疗的患者表达显著水平的β III-微管蛋白。这些发现得到了体外和体内环境的支持。我们的数据表明，β III-微管蛋白的表达在前列腺癌中通过雄激素去除而增加，并且这种β-微管蛋白亚型的表达与前列腺癌进展到去势抵抗状态相关，去势抵抗状态是前列腺癌死亡率的主要原因。
Class III β-tubulin (βIII-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 βIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, βIII-tubulin expression remains largely uncharacterised in prostate cancer. In this report, we evaluated the expression of βIII-tubulin in 138 different human prostate tumour specimens by immunohistochemistry from patients with hormone-treated or hormone-untreated prostate cancer. βIII-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. Whereas moderate-to-strong βIII-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 βIII-tubulin. These findings were supported by in vitro and in vivo settings. Our data indicate that βIII-tubulin expression is augmented in prostate cancer by androgen ablation and that the expression of this β-tubulin isoform is associated with the progression of prostate cancer to the castration-resistant state, a stage largely responsible for mortality from prostate cancer.