New therapy for renal cell carcinoma with down regulation of glycosyltransferase gene

下调糖基转移酶基因治疗肾细胞癌的新疗法

• 批准号: 17591676
• 负责人: ITO Akihiro
• 金额: $ 2.37万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591676/
• 关键词: renal cell carcinoma; glycolipid; ganglioside; Siglec-7; DSGb5; St6GalNAcVI; siRNA; cell motility; Silec-7; siRNA糖鎖合成酵素遺伝子

We have investigated changes of ganliosides in renal cell carcinoma (ROC) in regard to the malignant potential and found that the long chain gangliosides increased in metastasis, one of which is disialosyl globopentaosylceramide (DSGb5). The purpose of this project is to clarify the functional role of DSGb5. We have identified that 2,6-sialyltransferase (ST6GalNAcVI) catalyzes transfer of sialic acid to monosialosyl globopentaosylceramide (MSGb5) to synthesizes DSGb5. Down-regulation of ST6GalNAcVI mRNA by siRNA has led to decreases of motility of human renal cell carcinoma cells (ACHN cells) in vitro and decreases of cell growth of ACHN in nude mice. From these findings, DSGb5 has relevance to motility and growth of ACHN cells and down-regulation of ST6GalNac VI gene may become a new therapy for RCC.

我们研究了肾细胞癌(ROC)中甘露糖苷的变化与恶性潜能的关系，发现在转移过程中长链神经节苷脂增加，其中之一是二唾液酸糖基球戊糖神经酰胺(DSGb5)。本项目的目的是阐明DSGb5的功能作用。我们已经鉴定了2，6-唾液酸基转移酶(ST6GalNAcVI)催化唾液酸转移到单唾液糖基球状戊糖神经酰胺(MSGb5)以合成DSGb5。SiRNA下调ST6GalNAcVI基因的表达，导致体外培养的人肾癌细胞(ACHN细胞)活力下降，裸鼠ACHN细胞生长受阻。这些结果表明，DSGb5与ACHN细胞的运动和生长有关，下调ST6GalNac VI基因可能成为治疗肾癌的新方法。

项目成果

Current state and treatment strategy of renal cell carcinoma

肾细胞癌的现状及治疗策略

• 发表时间: 2006
• 期刊: Pharma Medica 24・11
• 作者: Arai Y;Hiroya N;Ito A;Kawamura S;Sato M
• 通讯作者: Sato M

Identification and expression of a sialyltransferase responsible for the synthesis of disialylglactosylgloboside in normal and malignant kidney cells : downregulation of ST6GalNAc VI in renal cancers.

负责正常和恶性肾细胞中二唾液酸乳糖基球苷合成的唾液酸转移酶的鉴定和表达：肾癌中 ST6GalNAc VI 的下调。

• 发表时间: 2007
• 期刊: Biochem J. 402・3
• 作者: Senda M;Ito A;Tsuchida A;Hagiwara T;Kaneda T;Nakamura Y;Frukawa K
• 通讯作者: Frukawa K

腎細胞癌の現状と治療戦略.

肾细胞癌的现状及治疗策略。

• 发表时间: 2006
• 期刊: Pharma Medica 24・11
• 作者: 荒井陽一;庵谷尚正;伊藤明宏;川村貞文;佐藤信
• 通讯作者: 佐藤信

Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: down-regulation of ST6GalNAc. VI in renalcancers.

负责正常和恶性肾细胞中二唾液酸半乳糖基球苷合成的唾液酸转移酶的鉴定和表达：ST6GalNAc 的下调。

• 发表时间: 2007
• 期刊: The Biochemical Journal 402
• 作者: Senda;M.
• 通讯作者: M.