The possibility of WT1 gene for new therapeutic target in ovarian cancer

WT1基因作为卵巢癌新治疗靶点的可能性

• 批准号: 24791680
• 负责人: OHTA Tsuyoshi
• 金额: $ 2.75万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24791680/
• 关键词: Wilms' tumor 1 (WT1); 卵巣癌; 腫瘍産生; VEGF; 血管新生; WT1 isoform; 腹水; Wilms' tumor 1; 発がん; 薬剤耐性

In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. In mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 -17AA/-KTS, disseminated tumor weights and production of ascites were significantly increased compared with those in mice inoculated with cells expressing the control vector. The overall survival in mice with WT1 -17AA/-KTS-expressing cells was significantly shorter than that in mice with control cells. WT1 -17AA/-KTS significantly increased the expression of vascular endothelial growth factor (VEGF) and tumor microvessel density compared with the control. These results indicated that WT1 -17AA/-KTS could enhance tumorigenic activity and could decrease patient survival through up-regulation of VEGF expression in ovarian cancers. The expression of WT1 -17AA/-KTS may induce ovarian cancer cells into a more aggressive phenotype.

在这项研究中，我们试图研究WT 1剪接变异体在体内卵巢癌模型中对致瘤活性和生存率的影响。在用表达WT 1 - 17 AA/-KTS的SKOV 3 ip 1细胞腹膜内接种的小鼠中，与用表达对照载体的细胞接种的小鼠相比，播散的肿瘤重量和腹水的产生显著增加。具有WT 1 - 17 AA/-KTS表达细胞的小鼠的总体存活率显著短于具有对照细胞的小鼠。与对照组相比，WT 1 - 17 AA/-KTS显著增加了血管内皮生长因子（VEGF）的表达和肿瘤微血管密度。这些结果表明，WT 1 - 17 AA/-KTS可通过上调卵巢癌中VEGF表达来增强致瘤活性并可降低患者存活率。WT 1 - 17 AA/-KTS的表达可能会诱导卵巢癌细胞形成更具侵袭性的表型。

项目成果

The role of YY1 in paclitaxel-induced cytotoxicity in epithelial ovarian cancer

YY1在紫杉醇诱导的上皮性卵巢癌细胞毒性中的作用

• 发表时间: 2012
• 作者: Ohta T;Ota T;Chien J;Shridhar V;Kurachi H
• 通讯作者: Kurachi H

子宮頸部神経内分泌癌6例の解析

宫颈神经内分泌癌6例分析

• 发表时间: 2014
• 期刊: 臨床婦人科産科
• 作者: 長谷川 歩美;太田 剛;倉智 博久
• 通讯作者: 倉智 博久

Non-sex cord-stromal ovarian tumors frequently produce and secrete estrogen in postmenopausal women : impact on bone metabolism and abnormal endometrial histology

非性索间质卵巢肿瘤经常在绝经后妇女中产生和分泌雌激素：对骨代谢和异常子宫内膜组织学的影响

• DOI: 10.1210/jc.2013-1267
• 发表时间: 2013
• 期刊: J Clin Endocrinol Metab
• 作者: Matsumura S;Ohta T;Takahashi T;T Kurachi H
• 通讯作者: T Kurachi H

卵巣癌におけるWT1 isoformの発現とその薬剤感受性に関する検討

WT1亚型在卵巢癌中的表达及其药物敏感性研究

• 发表时间: 2012
• 作者: Ohta T;Ota T;Chien J;Shridhar V;Kurachi H;太田剛
• 通讯作者: 太田剛

山形大学産科婦人科

山形大学妇产科