Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer.
Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer.
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DOI：
10.1002/cam4.32
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发表时间：
2012-10
期刊：
影响因子：
4
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Horio, Maiko;Kato, Takuya;Mii, Shinji;Enomoto, Atsushi;Asai, Masato;Asai, Naoya;Murakumo, Yoshiki;Shibata, Kiyosumi;Kikkawa, Fumitaka;Takahashi, Masahide
对铂类和紫杉烷类化疗的耐药性是卵巢癌治疗失败的主要原因。因此，有必要开发预测标记物和分子靶点来克服卵巢癌治疗中的耐药性。在之前的报告中，我们使用体外模型发现RET指蛋白（RFP）（也称为含三联基序的蛋白27，TRIM27）赋予癌细胞对抗癌药物的抵抗力。然而，RFP 表达在癌症患者中的意义仍然难以捉摸。在这项研究中，我们发现 RFP 在 62% 的卵巢癌患者中表达，其阳性率与耐药性显着相关。与临床数据一致，在卵巢癌细胞系 SKOV3 和 HEY 中通过 RNA 干扰 (RNAi) 消除 RFP，显着增加卡铂或紫杉醇诱导的细胞凋亡，并导致抗癌药物耐药性降低。在裸鼠肿瘤异种移植模型中，接种 RFP 敲低的卵巢癌细胞表现出比对照细胞更低的卡铂耐药性。这些发现表明 RFP 可能是卵巢癌患者化疗耐药的预测标志物，也是分子靶向药物的候选者。
Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. In a previous report, using an in vitro model, we found that the RET finger protein (RFP) (also known as tripartite motif-containing protein 27, TRIM27) confers cancer cell resistance to anticancer drugs. However, the significance of RFP expression in cancer patients remains elusive. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Consistent with clinical data, depletion of RFP by RNA interference (RNAi) in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin- or paclitaxel-induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients and also a candidate for a molecular-targeted agent.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
5.3
作者：
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影响因子：
82.9
作者：
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通讯作者：
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