Isolation of genomic instability genes that are associated with malignancy

与恶性肿瘤相关的基因组不稳定基因的分离

• 批准号: 20590309
• 负责人: SUZUKI Motoshi
• 金额: $ 3万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590309/
• 关键词: DNA複製; ゲノムインスタビリティー; 癌; DNA修復; 細胞周期; 肺癌; チェックポイント; マイクロアレー; ヒストン修飾; チェックポインイ

In examinations of 158 lung cancers and 5 mixtures of 10 normal lungs, cell cycle- and checkpoint-related genes generally showed mRNA expression increases in cancer, whereas POLD4 showed reduced mRNA in small cell lung cancer (SCLC). In the absence of POLD4, we observed defect in DNA repair activity, delay in cell cycle, and increased frequency of chromosomal break induction. Overexpression of an engineered POLD4 carrying silent mutations at the siRNA target site rescued these phenotypes, firmly establishing the role of POLD4 in these effects. In order to identify gene products that interact with POLD4, we performed an MS analysis using the immunoprecipitated protein fractions with POLD4, where ATM, CDC14 and other cell cycle checkpoint/progression proteins were detected. We further identified novel single nucleotide variations (SNV) in lung cancer cell lines. One of the SNV reduced the physical interaction ability with the catalytic subunit of pol delta. These results suggest that the newly identified SNV could be involved in the carcinogenesis by modifying DNA replication ability of DNA polymerase delta.

在检查158种肺癌和10种正常肺的5种混合物中，与细胞周期和检查点相关的基因通常显示癌症中的mRNA表达增加，而Pold4在小细胞肺癌（SCLC）中显示mRNA降低。在没有Pold4的情况下，我们观察到DNA修复活性，细胞周期延迟以及染色体断裂诱导频率的增加。在siRNA目标部位携带无声突变的工程pold4的过表达拯救了这些表型，牢固确定了Pold4在这些效果中的作用。为了鉴定与Pold4相互作用的基因产物，我们使用带有POLD4的免疫沉淀蛋白馏分进行了MS分析，其中检测到ATM，CDC14和其他细胞周期检查点/进展蛋白。我们进一步确定了肺癌细胞系中新型的单核苷酸变异（SNV）。 SNV之一降低了与Pol Delta的催化亚基的物理相互作用能力。这些结果表明，新鉴定的SNV可以通过修饰DNA聚合酶三角洲的DNA复制能力来参与癌变。

项目成果

Hyper-phosphorylated retinoblastoma protein suppresses telomere elongation

• DOI: 10.1271/bbb.70715
• 发表时间: 2008-02-01
• 期刊: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
• 影响因子: 1.6
• 作者: Takemura, Masaharu;Sugimura, Kazuto;Yoshida, Shonen
• 通讯作者: Yoshida, Shonen

let-7 regulates Dicer expression and constitutes a negative feedback loop

• DOI: 10.1093/carcin/bgn187
• 发表时间: 2008-11-01
• 期刊: CARCINOGENESIS
• 影响因子: 4.7
• 作者: Tokumaru, Shogo;Suzuki, Motoshi;Takahashi, Takashi
• 通讯作者: Takahashi, Takashi

Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF7, induced by anti-cancer drug, daunorubicin.

抗癌药物柔红霉素诱导的人乳腺癌细胞系 MCF7 中性鞘磷脂酶 2 基因表达的转录调控。

• 发表时间: 2009
• 期刊: Biochim Biophys Acta 1789
• 作者: Ito H.;et. al
• 通讯作者: et. al

Functions of base selection step in human DNA polymerase alpha.

人类 DNA 聚合酶 α 中碱基选择步骤的功能。

• 发表时间: 2010
• 期刊: DNA Repair (Amst). 9
• 作者: Tanaka S;Cao K;Niimi A;Limsirichaikul S;Miao HQ;Nakamura N;Murate T;Hasegawa Y;Takahashi T;Suzuki M.
• 通讯作者: Suzuki M.

肺癌とmiRNA

肺癌和 miRNA

• 发表时间: 2009
• 期刊: 実験医学 (印刷中)
• 作者: 細野祥之;鈴木元;高橋隆
• 通讯作者: 高橋隆