INSERM, Unité 955; Université Paris-Est, Faculté de Médecine; AP-HP, Groupe Henri Mondor-Albert Chenevier, Service d'Urologie, Département de Pathologie et Centre d'Investigations Biomédicales, Créteil, France.
Cancer Res. 2010 Nov 15;70(22):9253-64. doi: 10.1158/0008-5472.CAN-10-1447. Epub 2010 Nov 2.
Expression of class III β-tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe βIII-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated βIII-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, βIII-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of βIII-tubulin expression in human PCa cell lines using a human βIII-tubulin expression vector or βIII-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for βIII-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for βIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.
III 类β-微管蛋白（βIII-tubulin）的表达与几种人类恶性肿瘤的肿瘤进展和对紫杉烷类药物治疗的耐药性相关，但它作为前列腺癌（PCa）肿瘤行为的生物标志物的用途在很大程度上仍未得到探索。在这里，我们描述了来自广泛的 PCa 患者的前列腺肿瘤的βIII-tubulin 免疫组织化学染色模式，其中一些患者随后因去势抵抗性 PCa（CRPC）接受了多西紫杉醇治疗。在患有疑似局限性疾病的 PCa 患者中，βIII-tubulin 表达升高与肿瘤侵袭性显著相关，因为它被发现是治疗后生化复发的独立标志物。此外，对于接受多西紫杉醇为基础的化疗治疗 CRPC 的患者，肿瘤细胞中的βIII-tubulin 表达是总生存时间较低的独立预测因子。使用人βIII-tubulin 表达载体或βIII-tubulin 小干扰 RNA 对人 PCa 细胞系中的βIII-tubulin 表达进行操纵，以支持βIII-tubulin 表达作为 PCa 细胞对多西紫杉醇治疗耐药性的介导物的方式改变了细胞对多西紫杉醇治疗的存活。我们的研究结果表明，βIII-tubulin 可作为候选治疗性生物标志物，用于预测对多西紫杉醇为基础的化疗的反应，以及针对多西紫杉醇耐药性 CRPC 的治疗靶点。
