Mechanism of Tumor formation by deregulated circadian rhythm and strategy for its prevention

昼夜节律失调导致肿瘤形成的机制及预防策略

• 批准号: 20300229
• 负责人: OHTANI Naoko
• 金额: $ 12.23万
• 依托单位: Japanese Foundation For Cancer Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-20300229/
• 关键词: 生活習慣病; 概日リズム; 発癌; イメージング; p53; RB; p16; 慨日リズム

To clarify whether the deregulation of circadian rhythm is involved in cancer, DMBA (7,12-dimethylbenz[a]anthracene) treated mice of 4 or 5 days old were kept in the completely dark condition during day and night (Dark and Dark, DD) or in 12 h-light and 12 h-dark condition (Light and Dark, LD). After 30 weeks, mice were sacrificed, and the spectrum and the number of tumors were analyzed. Mice kept in DD condition developed significantly more lung tumors (3.9 fold more lung tumors in male mice and 2.1 fold more lung tumors in female mice). As a next step, the molecular mechanisms of how deregulation of circadian rhythm promotes lung tumors will be elucidated.

为了阐明昼夜节律失调是否与癌症有关，将 DMBA（7,12-二甲基苯并[a]蒽）治疗的 4 或 5 天大的小鼠保持在白天和夜间完全黑暗的条件下（Dark and Dark，DD）或 12 小时光照和 12 小时黑暗条件（Light and Dark，LD）。 30周后，处死小鼠，分析肿瘤谱和数量。处于 DD 条件下的小鼠出现明显更多的肺部肿瘤（雄性小鼠的肺部肿瘤多出 3.9 倍，雌性小鼠的肺部肿瘤多出 2.1 倍）。下一步，将阐明昼夜节律失调如何促进肺部肿瘤的分子机制。

项目成果

Real-time in vivo imaging of p16Ink4a reveals cross talk with p53.

P16INK4A的实时体内成像揭示了与p53的交叉对话。

• DOI: 10.1083/jcb.200904105
• 发表时间: 2009-08-10
• 期刊: The Journal of cell biology
• 作者: Yamakoshi K;Takahashi A;Hirota F;Nakayama R;Ishimaru N;Kubo Y;Mann DJ;Ohmura M;Hirao A;Saya H;Arase S;Hayashi Y;Nakao K;Matsumoto M;Ohtani N;Hara E
• 通讯作者: Hara E

Visualizing the dynamics of Oncogenic stress response in living mice.

可视化活体小鼠致癌应激反应的动态。

• 发表时间: 2009
• 作者: Laman;H.;Funes;J.;Ye;H.;Henderson;S.;Galinanes-Garcia;L.;Hara;E.;Knowles;P.;McDonald;N.;Boshoff;C.;Heike Laman;Kayoko Maehara;Naoko Ohtani
• 通讯作者: Naoko Ohtani

癌抑制機構としての細胞老化

细胞衰老作为一种癌症抑制机制

• 发表时间: 2009
• 作者: Goto;K.;et al.;大谷直子
• 通讯作者: 大谷直子

Real-time in vivo imaging of oncogenic stress response in living animals.

活体动物致癌应激反应的实时体内成像。

• 发表时间: 2009
• 作者: Goto;K.;et al.;大谷直子
• 通讯作者: 大谷直子

Real-time in vivo imaging of p16^<Ink4a> gene expression : a new approach to study senescence stress signaling in living animals.

p16^<Ink4a> 基因表达的实时体内成像：研究活体动物衰老应激信号传导的新方法。

• 发表时间: 2010
• 期刊: Cell Division 5:1
• 作者: Ohtani N;Yamakoshi K;Takahashi A;Hara E
• 通讯作者: Hara E