Function allotment analysis of the cold shock protein in a somatic cell and the generative cell

冷休克蛋白在体细胞和生殖细胞中的功能分配分析

• 批准号: 17590257
• 负责人: IZUMI Hiroto
• 金额: $ 2.18万
• 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 (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590257/
• 关键词: Cold shock protein; dbpA; dbpB; dbpC; YB-1; Contrin; Transcription factor; Gene expression; contrin

The result of this study is next (1)〜(7). (1)We analyzed molecular mechanism of the paclitaxel resistance in the breast cancer., As a result, it was thought that dbpB/YB-1 was the important molecule which participated in paclitaxel resistance in the breast cancer. (2) We made an antibody against dbpC/Contrin and examined the expression of normal and cancer tissue. As a result, it was suggested that dbpC/Contrin became a Cancer/Testis Antigen. (3) We examined the gene expression of dbpC/Contrin in the germ cell tumor and the localization in the cell. As a result, we identified an important lesion in the promoter and an important domain that controlled cellular localization in a C terminus of dbpC/Contrin. (4) YB-1 knock-out mice was embryonic lethal and exhibited exencephaly associated with reduction of β-Actin expression and F-actin formation. In addition, fibroblasts derived from YB-1 (-/-) embryos demonstrated reduced growth and cell density. These results demonstrated that YB-1 was involved in early mouse development. (5) We investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. It was suggested that Akt activation regulated the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. (6) We found that Twist was overexpressed in cisplatin-resistant cells, and it was suggested that YB-1 was a target gene of Twist and that YB-1 and Twist expression could induce tumor cell growth. (7) We found that Twist was associated with tumor suppressor gene product p53, and these interaction reduced p21 gene expression activated by p53 and YB-1 gene expression activated by Twist. Furthermore we clarified molecular mechanism of these transcriptional repressions.

这项研究的结果是下一个（1）和（7）。(1)We分析乳腺癌紫杉醇耐药的分子机制，因此，认为dbpB/YB-1是参与乳腺癌紫杉醇耐药的重要分子。(2)我们制备了抗dbpC/Bclin的抗体，并检测了正常组织和癌组织的表达。结果表明，dbpC/Ekalin成为癌/睾丸抗原。(3)我们检测了dbpC/cytokin基因在生殖细胞肿瘤中的表达及其在细胞中的定位。因此，我们确定了一个重要的病变的启动子和一个重要的结构域，控制细胞定位在C末端的dbpC/cytokin。(4)YB-1基因敲除小鼠具有胚胎致死性，并表现出与β-肌动蛋白表达和F-肌动蛋白形成减少相关的露脑畸形。此外，来自YB-1（-/-）胚胎的成纤维细胞表现出生长和细胞密度降低。这些结果表明，YB-1参与了小鼠的早期发育。(5)我们使用高密度寡核苷酸阵列研究了YB-1小干扰RNA（siRNA）转染卵巢癌细胞的表达谱。提示Akt的激活调控了YB-1的核转位，影响了卵巢癌细胞耐药基因及其他与卵巢癌恶性特征相关基因的表达。(6)我们发现Twist在顺铂耐药细胞中过表达，提示YB-1是Twist的靶基因，YB-1和Twist的表达可诱导肿瘤细胞生长。(7)我们发现Twist与肿瘤抑制基因产物p53相关，并且这些相互作用降低了由p53激活的p21基因表达和由Twist激活的YB-1基因表达。进一步阐明了这些转录抑制的分子机制。

项目成果

Twist and p53 reciprocally regulate target genes via direct interaction

• DOI: 10.1038/onc.2008.176
• 发表时间: 2008-09-18
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Shiota, M.;Izumi, H.;Kohno, K.
• 通讯作者: Kohno, K.

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

• DOI: 10.1038/sj.onc.1210084
• 发表时间: 2007-04-26
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Basaki, Y.;Hosoi, F.;Kuwano, M.
• 通讯作者: Kuwano, M.

Transcription factors and drug resistance

• DOI: 10.1016/j.ejca.2005.08.007
• 发表时间: 2005-11-01
• 期刊: EUROPEAN JOURNAL OF CANCER
• 影响因子: 8.4
• 作者: Kohno, K;Uchiumi, T;Izumi, H
• 通讯作者: Izumi, H

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: 10.1158/0008-5472.sabcs-09-1141
• 发表时间: 2009-12
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Tomoyuki Fujita;Ken-ichi Ito;H. Izumi;M. Kimura;M. Sano;H. Nakagomi;K. Maeno;Y. Hama;K. Shingū;S. Tsuchiya;K. Kohno;M. Fujimori

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