Three-dimensional collagen type I matrix up-regulates nuclear isoforms of the microtubule associated protein tau implicated in resistance to paclitaxel therapy in ovarian carcinoma.
Three-dimensional collagen type I matrix up-regulates nuclear isoforms of the microtubule associated protein tau implicated in resistance to paclitaxel therapy in ovarian carcinoma.
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DOI：
10.3390/ijms16023419
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发表时间：
2015-02-04
影响因子：
5.6
通讯作者：
Barbolina MV
中科院分区：
文献类型：
--
作者：
Gurler H;Yu Y;Choi J;Kajdacsy-Balla AA;Barbolina MV
上皮性卵巢癌是最致命的妇科恶性肿瘤。治疗失败的一个潜在原因是对紫杉醇的耐药性。微管相关蛋白tau的表达最近被认为是卵巢癌患者对紫杉醇反应的预测因子。使用免疫组织化学方法检测了312例原发性卵巢癌标本和40例转移性卵巢癌标本中tau的表达。采用Western blot和免疫荧光染色检测卵巢浆液性上皮癌细胞系中tau蛋白的表达。采用亚细胞分离和Western blot检测tau蛋白在细胞核和细胞质中的定位。基因沉默和克隆形成试验用于评价紫杉醇反应。Tau在所有测试病例中的44%中表达。在原发性浆液性上皮性卵巢癌病例中，46%为tau蛋白阳性。在转移性浆液性上皮性卵巢癌中，63%为tau阳性。细胞培养实验表明，tau蛋白以多种亚型表达。三维I型胶原基质培养条件导致tau蛋白的上调。在三维培养条件下用特异性siRNA沉默tau导致用紫杉醇处理的细胞的克隆形成能力显著降低。这些数据表明，tau蛋白表达的减少可能使卵巢癌对紫杉醇治疗敏感。
Epithelial ovarian carcinoma is the deadliest gynecologic malignancy. One reason underlying treatment failure is resistance to paclitaxel. Expression of the microtubule associated protein tau has recently been proposed as a predictor of response to paclitaxel in ovarian carcinoma patients. Expression of tau was probed using immunohistochemistry in 312 specimens of primary, and 40 specimens of metastatic, ovarian carcinoma. Serous epithelial ovarian carcinoma cell line models were used to determine the expression of tau by Western blot and immunofluorescence staining. Subcellular fractionation and Western blot were employed to examine nuclear and cytoplasmic localization of tau. Gene silencing and clonogenic assays were used to evaluate paclitaxel response. Tau was expressed in 44% of all tested cases. Among the primary serous epithelial ovarian carcinoma cases, 46% were tau-positive. Among the metastatic serous epithelial ovarian carcinomas, 63% were tau-positive. Cell culture experiments demonstrated that tau was expressed in multiple isoforms. Three-dimensional collagen I matrix culture conditions resulted in up-regulation of tau protein. Silencing of tau with specific siRNAs in a combination with three-dimensional culture conditions led to a significant decrease of the clonogenic ability of cells treated with paclitaxel. The data suggest that reduction of tau expression may sensitize ovarian carcinoma to the paclitaxel treatment.
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影响因子：
3.4
作者：
He, Wenting;Zhang, Dachuan;Wu, Changping
通讯作者：
Wu, Changping
影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
11.5
作者：
Andre, Fabrice;Hatzis, Christos;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
11.4
作者：
GOEDERT, M;JAKES, R
通讯作者：
JAKES, R
胃癌中 tau 表达的减少可以确定紫杉醇治疗成功的候选者。
影响因子：
8.8
作者：
Mimori, K.;Sadanaga, N.;Yoshikawa, Y.;Ishikawa, K.;Hashimoto, M.;Tanaka, F.;Sasaki, A.;Inoue, H.;Sugimachi, K.;Mori, M.
通讯作者：
Mori, M.