Taxol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III β-tubulin
Taxol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III β-tubulin
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DOI：
10.1097/pgp.0b013e318156c838
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发表时间：
2008-04-01
影响因子：
2.4
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Umezu, Tomokazu;Shibata, Kiyosumi;Kikkawa, Fumitaka
组织学在上皮性卵巢癌(EOC)中的预后意义已得到充分证实。透明细胞和粘液组织学尤其被普遍接受，因为它们对化疗的反应很差，会导致不良结果。以前的报告表明，III类β-微管蛋白诱导紫杉醇耐药与减少微管动态不稳定性的影响有关。因此，本研究旨在评估III类β-微管蛋白的表达，并检查III类β-微管蛋白的蛋白水平是否与化疗敏感性的组织学差异有关。免疫组织化学方法将80例卵巢癌组织中III类β-微管蛋白表达分为4组(-、+/-、+、++)。在35例透明细胞癌、8例粘液性癌、5例子宫内膜样癌和5例浆液性癌中，高表达(+，++)III类β-微管蛋白。19名患者的反应是可评估的。在5名应答者中，未检测到高水平的III类β-微管蛋白表达。另一方面，在14名无反应者中有10人检测到了它。在一些卵巢癌细胞系中，我们通过Western印迹分析评估了III类β-微管蛋白的表达。III型β-微管蛋白在非浆液性癌中的表达高于浆液性癌。与野生型SKOV细胞相比，紫杉醇耐药的SKOV细胞显示高水平的III型β-微管蛋白表达。卵巢上皮性癌不同组织亚型对紫杉醇的敏感性与III类β-微管蛋白的表达有关。
The prognostic significance of histology has been well established in epithelial ovarian cancer (EOC). Clear cell and mucinous histologies are especially generally accepted to result in an adverse outcome because of their poor chemotherapy response. Previous reports suggested that class III beta-tubulin induced taxol resistance in association with a reduced effect on microtubule dynamic instability. Thus, this study aimed to evaluate class III beta-tubulin expression and examine whether the protein level of class III beta-tubulin was correlated with the histological difference in chemosensitivity. Class III beta-tubulin expression in EOC tissues (n = 80) was immunohistochemically scored into 4 groups (-, +/-, +, ++). High-level (+, ++) class III beta-tubulin expression was detected in 30 of 35 clear cell carcinomas, in 8 of 10 mucinous carcinomas, 5 of 11 endometrioid carcinomas, and 5 of 24 serous carcinomas. Nineteen patients were evaluable for response. In 5 responders, high-level class III beta-tubulin expression was not detected. On the other hand, it was detected in 10 of 14 nonresponders. In some ovarian cancer cell lines, we evaluated class III beta-tubulin expression by Western blot analysis. Class III beta-tubulin expression in nonserous carcinoma tended to be higher than that in serous carcinoma. Taxol-resistant SKOV cells showed high-level class III beta-tubulin expression compared with wild-type SKOV cells. Taxol sensitivity differing among histological subtypes in EOC is associated with the expression of class III beta-tubulin.