The exploration of novel therapeutic target in gastric cancer by comprehensive tyrosine-kinase analysis

酪氨酸激酶综合分析探索胃癌新治疗靶点

• 批准号: 23591930
• 负责人: YAMASAKI Makoto
• 金额: $ 3.24万
• 依托单位: Osaka 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-23591930/
• 关键词: 胃癌; チロシンキナーゼ; 腹膜播種; 網羅的発現解析; 化学療法感受性

We analyzed the comprehensive gene expression in gastric cancer to explore the novel tyrosine-kinase related to the development of cancer, especially peritoneal dissemination. Then the novel and well-known tyrosine-kinases; KSR1 and MEK, Her2 and FGFR1 were identified. KSR1 is a tyrosine-kinase that functions as positive regulator of Ras pathway, and associated with the cell motility, invasion and peritoneal dissemination. FOXM1, DOK2 and REGIV are identified as the downstream molecules of the tyrosine-kinases, MEK, Her2 and FGFR1, respectively in consequence of the analysis of the correlativity between the pathways of these tyrosine-kinases and gene expression analysis. It was shown that these molecules related with the prognosis, peritoneal dissemination and the sensitivity of anticancer drug.This result may enable us to elucidate the signaling related to the biological character of gastric cancer and develop the novel molecular-targeted agent.

我们分析了胃癌的综合基因表达，以探索与癌症发展，特别是腹膜播散相关的新型酪氨酸激酶。然后是新颖且众所周知的酪氨酸激酶；鉴定出 KSR1 和 MEK、Her2 和 FGFR1。 KSR1 是一种酪氨酸激酶，作为 Ras 通路的正调节因子，与细胞运动、侵袭和腹膜播散相关。通过对这些酪氨酸激酶通路之间的相关性分析和基因表达分析，FOXM1、DOK2和REGIV分别被确定为酪氨酸激酶MEK、Her2和FGFR1的下游分子。结果表明，这些分子与预后、腹膜播散和抗癌药物的敏感性有关。这一结果可能使我们能够阐明与胃癌生物学特性相关的信号传导并开发新型分子靶向药物。