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CCNDBP1はATM-CHK2経路を介したDNA損傷に応答する
http://hdl.handle.net/10191/0002000824
http://hdl.handle.net/10191/00020008240ae953da-2938-4c71-ae9b-df53d5fab74d
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本文 (1.89MB)
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要旨 (561KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2023-03-07 | |||||||||
| タイトル | ||||||||||
| タイトル | Cyclin D1 binding protein 1 responds to DNA damage through the ATM–CHK2 pathway | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | CCNDBP1はATM-CHK2経路を介したDNA損傷に応答する | |||||||||
| 言語 | ja | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Ccndbp1 | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Atm | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Ezh2 | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Chk2 | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | DNA damage | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | hepatocellular carcinoma | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| 資源タイプ | doctoral thesis | |||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| その他のタイトル | ||||||||||
| その他のタイトル | CCNDBP1 and the ATM–CHK2 pathway | |||||||||
| 言語 | en | |||||||||
| 著者 |
丹羽, 佑輔
× 丹羽, 佑輔
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Background: Since CCNDBP1 is a cyclin D-binding dominantly-negative helix-loop-helix protein that is expressed in various tissues, it is considered a tumor suppressor, as it negatively regulates TGF-β signal-induced cell migration depending on the surrounding condition. When expressed in tumor cells, CCNDBP1 can contribute to the viability of cancer cells by rescuing them from chemotherapy-induced DNA damage. Therefore, this study focused on investigating the function of CCNDBP1, which is directly related to survival from DNA damage and chemoresistance in cancer cells. Methods: Molecular mechanisms of CCNDBP1 related to the recovery from DNA damage were examined in vitro and in vivo, using hepatocellular carcinoma (HCC) cells and tissues obtained from Ccndbp1 knockout mice. X-ray irradiation was then used to induce DNA damage. Subsequently, gene and protein expression changes associated with CCNDBP1's upregulation, downregulation, and irradiation were assessed. Results: As observed, CCNDBP1's overexpression in HCC cells stimulated cell growth and showed resistance to X-ray irradiation. Gene expression analyses of CCNDBP1-overexpressed cells and Ccndbp1 knockout mice revealed that Ccndbp1 inhibitory dependently controlled the expression of Ezh2. However, irradiation Ccndbp1-dependently decreased Ezh2's expression. Further analyses of DNA damage-related protein expressions in vitro and in vivo also showed that Ccndbp1 activated the Atm-Chk2 pathway through the inhibition of Ezh2 expression, thereby accounting the resistance to DNA damage. Conclusions: Our study, therefore, demonstrated that by inhibiting EZH2, CCNDBP1 contributed to the activation of the ATM-CHK2 pathway to alleviate DNA damage, leading to chemoresistance. | |||||||||
| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | Journal of clinical medicine. 2022, 11(3), 851. | |||||||||
| 言語 | en | |||||||||
| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.3390/jcm11030851 | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 13101 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 新潟大学 | |||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Niigata University | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2022-03-23 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第4968号 | |||||||||
| 学位記番号 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 新大院博(医)第1038号 | |||||||||
| 言語 | ja | |||||||||
