The role of ALKBH family in bladder cancer development

ALKBH 家族在膀胱癌发生中的作用

• 批准号: 23590471
• 负责人: SHIMADA Keiji
• 金额: $ 3.24万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-23590471/
• 关键词: urothelial carcinoma; ALKBH3; ROS; Tweak; Fn14; VEGF; reactive oxygen species; 膀胱癌; 活性酸素種; NADPH oxidase; Reactive oxygen species; Urothelial carcinoma

The role and function of ALKBH3 in human urothelial carcinoma development were examined. ALKBH3 knockdown induced cell cycle arrest at the G1 phase through downregulation of NOX-2-mediated generation of ROS. ALKBH3 knockdown reduced VEGF expression by reducing expression of Tweak and its receptor, Fn14. Silencing of ALKBH3 or Tweak significantly suppressed invasion and angiogenesis of urothelial carcinoma in vivo . Interestingly, not only urothelial carcinoma cells but also vascular endothelial cells within cancer foci expressed Fn14, which was strongly reduced by ALKBH3 and Tweak knockdown in vivo, suggesting that ALKBH3-dependent expression of Tweak stabilizes Fn14. Immunohistochemical examination showed high expression of ALKBH3, Tweak, and Fn14 in urothelial carcinoma, especially in high-grade, invasive carcinomas; moreover, Fn14-positive vessel counts within cancer foci were increased in invasive phenotypes. ALKBH3 contributes to development of urothelial carcinomas.

探讨了ALKBH3在人尿路上皮癌发生发展中的作用和功能。ALKBH3敲低通过下调nox -2介导的ROS生成诱导细胞周期阻滞在G1期。ALKBH3敲除通过降低Tweak及其受体Fn14的表达来降低VEGF的表达。沉默ALKBH3或Tweak可显著抑制尿路上皮癌的侵袭和血管生成。有趣的是，除了尿路上皮癌细胞外，癌灶内的血管内皮细胞也表达Fn14，而Fn14在体内被ALKBH3和Tweak敲低强烈降低，表明Tweak依赖ALKBH3的表达稳定了Fn14。免疫组化检查显示ALKBH3、Tweak和Fn14在尿路上皮癌中高表达，特别是在高级别浸润性癌中；此外，在侵袭性表型中，癌灶内fn14阳性血管计数增加。ALKBH3参与尿路上皮癌的发展。

项目成果

ヒト膀胱癌におけるMUC1発現制御を介したALKBH2の役割

ALKBH2 在调节人膀胱癌 MUC1 表达中的作用

• 发表时间: 2013
• 作者: 藤井智美;島田啓司;穴井智;藤本清秀;小西登
• 通讯作者: 小西登

膀胱癌における血管新生因子Tweak/Fn14発現の病理学的意義について

膀胱癌中血管生成因子Tweak/Fn14表达的病理意义

• 发表时间: 2012
• 作者: 島田啓司;藤井智美;穴井智;藤本清秀;小西登
• 通讯作者: 小西登

ALKBH3 contributes to angiogenesis of human urothelial carcinoma cells through Tweak/Fn14 signal

ALKBH3 通过 Tweak/Fn14 信号促进人尿路上皮癌细胞的血管生成

• 发表时间: 2012
• 作者: Keiji Shimada;Tomomi Fujii;Satoshi Anai;Kiyohide Fujimoto;Noboru Konishi
• 通讯作者: Noboru Konishi

膀胱尿路上皮癌進展にかかわる新規分子メカニズムの解析

膀胱尿路上皮癌进展的新分子机制分析

• 发表时间: 2011
• 作者: Okada F and Kobayashi H;(Eds. D Lyden;DR Welch and B Psaila);島田啓司
• 通讯作者: 島田啓司

ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer.

• DOI: 10.1038/sj.bjc.6606012
• 发表时间: 2011-02-15
• 期刊: British journal of cancer
• 影响因子: 8.8