Interaction of molecules with VHL-signaling pathway in renal cell carcinoma

肾细胞癌中分子与 VHL 信号通路的相互作用

• 批准号: 23791795
• 负责人: YOSHIDA Takeshi
• 金额: $ 2.66万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791795/
• 关键词: ＶＨＬ; ＨＩＦ; Ｔｗｉｓｔ; ＥＭＴ; 腎細胞癌; HIF; VHL; EMT; Twist; RCC; VEGF; HRE

In this study, we focused on Twist, which is involved in EMT (epithelial-mesenchymal transition) and demonstrated its effect on VHL-HIF signaling pathway.Transcriptional activity of VEGF by Twist was measured by reporter assay using HIF responsive element (HRE) reporter plasmids co-transfected with Twist expression plasmid. Overexpressed Twist activated HRE reporter activity. VEGF promoter activity was activated by Twist in hypoxia.Binding of Twist to VEGF promoter in tumor cells were shown by chromatin immunoprecipitation (ChIP) assay using antibody against Twist. ChIP assay showed Twist binding to VEGF promoter. Electrophoresis Mobility Shift Assay (EMSA) were demonstrated to show binding of Twist for specific sequence (about -1000bp upstream from start point of transcription) in VEGF promoter.These data suggest that Twist expression involves in tumor vascularization in renal tumor.

本研究以Twist为靶点，通过共转染HIF应答元件（HRE）报告质粒，检测Twist对VEGF的转录活性，探讨Twist对VHL-HIF信号通路的影响。过表达的Twist激活HRE报告基因活性。缺氧条件下Twist可激活VEGF启动子活性，抗Twist抗体染色质免疫沉淀法（ChIP）检测Twist与肿瘤细胞VEGF启动子的结合。ChIP分析显示Twist与VEGF启动子结合。电泳迁移率改变实验（EMSA）显示Twist与VEGF启动子上游约-1000bp的特异序列结合，提示Twist的表达与肾肿瘤血管形成有关。

项目成果

独立して発症した組織の異なる腎細胞癌の免疫組織学的検討

独立发展的不同组织学肾细胞癌的免疫组织化学检查

• 作者: 吉田毅;松本哲朗
• 通讯作者: 松本哲朗

Twist up-regulates VEGF expression with HIF in hypoxia

Twist 在缺氧条件下利用 HIF 上调 VEGF 表达

• 发表时间: 2014
• 作者: Takeshi Yoshida;Ryoichi Hamasuna;Naohiro Fujimoto;Tetsuro Matsumoto
• 通讯作者: Tetsuro Matsumoto

Three cases of Plasmacytoid variant of Bladder tumor

浆细胞样变异型膀胱肿瘤三例

• 发表时间: 2013
• 作者: Takeshi Yoshida;Ryoichi Hamasuna;Naohiro Fujimoto;Tetsuro Matsumoto
• 通讯作者: Tetsuro Matsumoto

尿路上皮癌における亜型組織の病理組織学的検討

尿路上皮癌亚型的组织病理学检查

• 作者: 吉田毅;藤本直浩;松山篤司;松本哲朗
• 通讯作者: 松本哲朗

腎細胞癌のサブタイプにおけるEMTマーカーの発現の検討

肾细胞癌亚型中 EMT 标志物表达的检测

• 发表时间: 2013
• 作者: 吉田毅;浜砂良一;藤本直浩;松本哲朗
• 通讯作者: 松本哲朗