Diagnostic and therapeutic application of checkpoint gene T-fimbrin in gastrointestinal

检查点基因T-fimbrin在胃肠道诊断和治疗中的应用

• 批准号: 16590609
• 负责人: SASAKI Yasushi
• 金额: $ 2.62万
• 依托单位: Sapporo 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590609/
• 关键词: T-fimbrin; DNA damage; DNA methylation; Cell Cycle Control; Chemosensitivity; Actin binding protein; Liver cancer

Fimbrins (also known as plastins) are actin-binding proteins of the cortical cytoskeleton present in all cells and conserved from yeast to mammals. We previously reported that the upregulation of T-fimbrin, a fimbrin isoform, in association with G2 arrest following DNA damage and that a lack of T-fimbrin expression shortens the radiation-induced G2 arrest in Chinese hamster ovarian cells [Y.Sasaki et al. (2002) Int.J.Cancer, 97, 211-216]. In this study, we further investigated the role of T-fimbrin in DNA damage response using a panel of human liver cancer cell lines and small interfering RNA technology. T-fimbrin was differentially expressed in human liver cancer cell lines. Colony formation assays revealed that cell lines lacking T-fimbrin expression were highly sensitive to DNA damage compared to cell lines that express T-fimbrin. Using siRNA designed to target T-fimbrin, we demonstrated that silencing endogenous T-fimbrin causes a marked increase in the cellular sensitivity to VP-16 and UV irradiation. Moreover, T-fimbrin deletion abrogated UV-mediated cell cycle checkpoint, and consequently led to increased apoptotic cell death in resistant cells. These findings suggest that the status of T-fimbrin expression may be a useful molecular marker for predicting the responsiveness of cancer cells to treatment with chemotherapeutic drugs.

Fimbrins(也称为plastins)是存在于所有细胞中的皮质细胞骨架的肌动蛋白结合蛋白，从酵母到哺乳动物都是如此。我们之前曾报道，在DNA损伤后，纤毛蛋白亚型T-fimbrin的上调与G2期停滞有关，并且T-Fimbrin表达的缺失缩短了辐射诱导的中国仓鼠卵巢细胞G2期停滞[Y.Sasaki等人]。(2002)国际癌症杂志，97,211-216]。在这项研究中，我们利用一组人肝癌细胞系和小干扰RNA技术，进一步研究了T-fimbrin在DNA损伤反应中的作用。T-fimbrin在人肝癌细胞系中差异表达。克隆形成实验表明，与表达T-fimbrin的细胞株相比，缺乏T-fimbrin表达的细胞系对DNA损伤高度敏感。利用针对T-fimbrin的siRNA，我们证明了沉默内源性T-fimbrin导致细胞对VP-16和UV辐射的敏感性显著增加。此外，T-fimbrin缺失取消了紫外线介导的细胞周期检查点，从而导致耐药细胞中凋亡细胞死亡的增加。这些发现表明，T-fimbrin的表达状态可能是预测癌细胞对化疗药物治疗反应的有用的分子标志物。

项目成果

Activation of the ribosomal protein L13 gene in human gastrointestinal cancer.

• DOI: 10.3892/ijmm.18.1.161
• 发表时间: 2006-07
• 期刊: International journal of molecular medicine
• 影响因子: 5.4
• 作者: Toshihisa Kobayashi;Y. Sasaki;Yuichiro Oshima;Hiroyuki Yamamoto;H. Mita;Hiromu Suzuki;M. Toyota

The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer

• DOI: 10.1053/j.gastro.2005.03.051
• 发表时间: 2005-07-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Akino, K;Toyota, M;Tokino, T
• 通讯作者: Tokino, T

Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer.

• 发表时间: 2005-02
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: M. Murai;M. Toyota;Hiromu Suzuki;A. Satoh;Y. Sasaki;K. Akino;M. Ueno;F. Takahashi;M. Kusano;H. Mita;K. Yanagihara;T. Endo;Y. Hinoda;T. Tokino;K. Imai

Abnormal beta-catenin expression in oral cancer with no gene mutation: correlation with expression of cyclin D1 and epidermal growth factor receptor, Ki-67 labeling index, and clinicopathological features.

无基因突变口腔癌β-连环蛋白表达异常：与细胞周期蛋白D1和表皮生长因子受体表达、Ki-67标记指数及临床病理特征的相关性。

• 发表时间: 2005
• 期刊: H u m P a t h o l 36(3)
• 作者: Odajima T;Sasaki Y;Tanaka N;Kato-Mori Y;Asanuma H;Ikeda T;Satoh M;Hiratsuka H;Tokino T;Sawada N
• 通讯作者: Sawada N

Identification of a specific target sequence for p53 family in the Jagged2 gene.

鉴定 Jagged2 基因中 p53 家族的特定靶序列。

• 期刊: Tumor Research (in press)
• 作者: Sasaki Y;et al.;Murai M;Murai M;Sasaki Y;Sasaki Y;Satoh A;Ueno M;Sasaki Y et al.;Satoh A et al.;Ueno M et al.;Ueno M;Sasaki Y;Satoh A;Kobayashi T;Oshima Y
• 通讯作者: Oshima Y