Cellular responses against DNA damage and search for novel molecular target

细胞对 DNA 损伤的反应和寻找新的分子靶点

• 批准号: 17016075
• 负责人: KOHNO Kimitoshi
• 金额: $ 27.14万
• 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 Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17016075/
• 关键词: DNA損傷; 遺伝子発現制御; YB-1; ZNF143; Clock; Tip60; Wnt10A; シスプラチン; RFK; Twist; FOX03; Ets; ペロキシレドキシン; STAT3; HMGB1; シグナル伝達; 概日リズム; ATF4; DNA

Based on the analysis of drug resistant cells, we found several molecular targets such as YB-1, ZNF143, Clock and so on. These molecules are useful for cancer treatment. Molecular clocks in peripheral tissues control cell-proliferation rhythms by regulating the expression of cell-cycle genes. We also found the novel Wnt signaling pathway by which circadian disruption can induce malignant progression of tumor through angio/stromagenesis.

通过对耐药细胞的分析，我们发现了YB-1、ZNF 143、Clock等分子靶点，这些分子对肿瘤的治疗具有重要意义。外周组织中的分子钟通过调节细胞周期基因的表达来控制细胞增殖节律。我们还发现了新的Wnt信号通路，通过该通路，昼夜节律紊乱可以通过血管/基质形成诱导肿瘤的恶性进展。

项目成果

Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel

• DOI: 10.1158/1078-0432.ccr-05-0945
• 发表时间: 2005-12-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Fujita, T;Ito, KI;Fujimori, M
• 通讯作者: Fujimori, M

Stimulation of NEIL2-mediated Oxidized Base Excision Repair via YB-1 Interaction duiring Oxidative Stress

氧化应激期间通过 YB-1 相互作用刺激 NEIL2 介导的氧化碱基切除修复

• 发表时间: 2007
• 期刊: J. Biol. Chem. 282
• 作者: Das;S.
• 通讯作者: S.

Clock/ATF4 transcription system regulates drug resistance in human cancer cell lines

时钟/ATF4转录系统调节人类癌细胞系的耐药性

• 发表时间: 2007
• 期刊: Oncogene (in press)
• 作者: Igarashi;T.
• 通讯作者: T.

Fragmented hyaluronan induces transcriptional up-regulation of the multidrug resistance-1 gene in CD4+T cells

片段化透明质酸诱导 CD4 T 细胞中多药耐药性 1 基因转录上调

• 发表时间: 2006
• 期刊: J. Biol. Chem. 281・49
• 作者: Tsujimura;S.
• 通讯作者: S.

Roles of volume-sensitive Cl- channel in cisplatin-induced apoptosis in human epidermoid cancer cells

• DOI: 10.1007/s00232-005-0779-y
• 发表时间: 2005-06-01
• 期刊: JOURNAL OF MEMBRANE BIOLOGY
• 影响因子: 2.4
• 作者: Ise, T;Shimizu, T;Okada, Y
• 通讯作者: Okada, Y