Gene expression profiles with cDNA microarray reveal RhoGDI as a predictive marker for paclitaxel resistance in ovarian cancers.
Gene expression profiles with cDNA microarray reveal RhoGDI as a predictive marker for paclitaxel resistance in ovarian cancers.
复制标题
DOI：
10.3892/or.15.5.1265
复制
发表时间：
2006-05
期刊：
影响因子：
4.2
通讯作者：
T. Goto;M. Takano;M. Sakamoto;A. Kondo;J. Hirata;T. Kita;H. Tsuda;Y. Tenjin;Y. Kikuchi
中科院分区：
文献类型：
--
作者：
T. Goto;M. Takano;M. Sakamoto;A. Kondo;J. Hirata;T. Kita;H. Tsuda;Y. Tenjin;Y. Kikuchi
在本研究中，我们通过比较紫杉醇耐药和亲本卵巢癌细胞系的基因表达谱，鉴定了紫杉醇耐药相关基因。采用基因芯片技术，对KF28和KFr13暴露于紫杉醇中诱导的人卵巢癌细胞系KF28、顺铂耐药细胞系KFr13和紫杉醇耐药细胞系KF28TX和KFr13TX的基因表达谱进行了比较和分析。比较557个人类癌症相关cDNA转录物，在紫杉醇耐药的KF28TX中发现5个基因过表达，5个基因过表达，而另一个紫杉醇耐药的KFr13TX有5个基因过表达，8个基因过表达。在这些基因中，atp结合盒亚家族（MDR-1）、Rho鸟嘌呤二核苷酸磷酸解离抑制剂β (RhoGDI)和胰岛素样生长因子结合蛋白3 （IGFBP-3）在两种紫杉醇耐药细胞系中均有过表达。通过实时定量PCR，我们确认了阵列结果。因此，我们认为IGFBP-3、RhoGDI和MDR-1与紫杉醇耐药相关。此外，对接受紫杉醇化疗的22例浆液性卵巢癌组织进行免疫组织化学染色分析，发现无反应者的RhoGDI过表达频率高于反应者（p=0.004）。RhoGDI的表达不仅在紫杉醇耐药细胞系中，而且在临床样品中被证明是紫杉醇耐药的预测指标。
In the current study, we identified paclitaxel-resistant related genes by comparing gene expression profiles of paclitaxel-resistant and parent ovarian cancer cell lines. Gene expression profiles of the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel were compared and analyzed using cDNA microarray. Of 557 human cancer-related cDNA transcripts compared, 5 genes were found to be underexpressed and 5 genes overexpressed in the paclitaxel-resistant KF28TX, while another paclitaxel-resistant KFr13TX had 5 underexpressed and 8 overexpressed genes. Among these genes, overexpression of the ATP-binding cassette subfamily (MDR-1), Rho guanine dinucleotide phosphate dissociation inhibitor beta (RhoGDI) and insulin-like growth factor binding protein 3 (IGFBP-3) was observed in both paclitaxel-resistant cell lines. Using real-time quantitative PCR, we confirmed the array results. We therefore conclude that IGFBP-3, RhoGDI and MDR-1 were correlated with paclitaxel resistance. Moreover, immunohistochemical staining was analyzed in 22 serous ovarian cancer tissues from patients who received paclitaxel-based chemotherapy, and RhoGDI overexpression was observed more frequently in non-responsers than in responders (p=0.004). RhoGDI expression proved to be a predictive marker of paclitaxel resistance not only in paclitaxel-resistant cell lines, but also in clinical samples.