WEKO3
アイテム
Study on the negative regulators of IKKβ/NF-κB focusing on the link between inflammation and cancer
http://hdl.handle.net/10212/2192
http://hdl.handle.net/10212/21920142c3ed-0040-4d6a-ba8f-348fc4a6b378
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
全文 (16.1 MB)
|
|
|
|
内容・審査結果の要旨 (327.1 KB)
|
|
| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2015-09-17 | |||||||||
| タイトル | ||||||||||
| タイトル | Study on the negative regulators of IKKβ/NF-κB focusing on the link between inflammation and cancer | |||||||||
| 言語 | en | |||||||||
| その他のタイトル | ||||||||||
| その他のタイトル | 炎症と癌の関連に注目した IKKβ/NF-κ抑制メカニズムの研究 | |||||||||
| 言語 | ja | |||||||||
| 作成者 |
グエン ティエン, ダット
× グエン ティエン, ダット
|
|||||||||
| 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 | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Inflammation | |||||||||
| 主題 | ||||||||||
| 言語 | ja | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | NF-κB | |||||||||
| 主題 | ||||||||||
| 言語 | ja | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | IKKβ | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | AMAP1 | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | cancer | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | aspirin | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | NF-kB is a major transcriptional factor regulating many cellular functions including inflammation; and its role is a pivotal link between inflammation an cancer. Therefore, its appropriate control is of high importance. In this study, we showed a novel negative regulator of IKKb, an essential kinase in NF-kB signaling; and a novel mechanism in that an anti-inflammatory medicine, aspirin protects against cancer via IKKb/NF-kB. First, AMAP1 was showed as a negative feedback regulator for NF-kB by binding with IKKb. Proteomics analysis identified AMAP1 as a binding protein with IKKb. Overexpression of AMAP1 suppressed NF-kB activity by interfering the binding of IKKb and NEMO, and deletion of AMAP1 augmented NF-kB activity. The activation of NF-kB induced translocation of AMAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of AMAP1 and IKKb. These results demonstrated a advanced role of AMAP1 as a negative feedback regulator of NF-kB, and presented it as a possible target for anti-inflammatory treatments. Second, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis. Interestingly, the analysis identified APC as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumorsuppressing gene which can cause colorectal cancer when it is mutated. Previous reports indicated that aspirin specifically inhibits IKKb activity, and constitutively active form of IKKb accelerates APC loss. We found that aspirin suppressed the expression of IKKb, and the deletion of IKKb by siRNA increases the expression of APC in HEK294 cells and HUVECs. These results reveal that aspirin up-regulates the expression of APC via the suppression of IKKb, which can be a mechanism how aspirin prevents cancer at least in part. | |||||||||
| 言語 | en | |||||||||
| 日付 | ||||||||||
| 日付 | 2014-09-25 | |||||||||
| 日付タイプ | Issued | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| 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 | |||||||||
| 出版タイプ | ||||||||||
| 出版タイプ | VoR | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第718号 | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（学術） | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2014-09-25 | |||||||||
| 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 | 14303 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 京都工芸繊維大学 | |||||||||
