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潜在的な治療標的SCG2は、スニチニブ耐性腎細胞癌においてHIF1αと連携する可能性がある
http://hdl.handle.net/10232/0002000155
http://hdl.handle.net/10232/000200015513a5d588-478f-48ca-aa5e-7fe0f7782b66
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2024-02-29 | |||||
| タイトル | ||||||
| タイトル | Potential therapeutic target secretogranln II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| タイトル | 潜在的な治療標的SCG2は、スニチニブ耐性腎細胞癌においてHIF1αと連携する可能性がある | |||||
| タイトル言語 | ja | |||||
| 著者 |
福元, 渉
× 福元, 渉 |
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| 言語 | ||||||
| 言語 | eng | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | angiogenesis | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | HIF1α | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | renal cell carcinoma | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | SCG2 | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | sunitinib resistance | |||||
| 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 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Multitargeted receptor tyrosine kinase inhibitors, including vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib, have been used as the primary targeted agents for patients with recurrent or distant metastasis of advanced renal cell carcinoma (RCC). However, endogenous or acquired sunitinib resistance has become a significant therapeutic problem. Therefore, we focused on mechanisms of sunitinib resistance in RCC. First, we undertook RNA sequencing analysis using previously established sunitinib-resistant RCC (SUR-Caki1, SUR-ACHN, and SUR-A498) cells. The results showed increased expression of secretogranin II (SCG2, chromogranin C) in SUR-RCC cells compared to parental cells. The Cancer Genome Atlas database showed that SCG2 expression was increased in RCC compared to normal renal cells. In addition, the survival rate of the SCG2 high-expression group was significantly lower than that of the RCC low-expression group. Thus, we investigated the involvement of SCG2 in sunitinib-resistant RCC. In vitro analysis showed that migratory and invasive abilities were suppressed by SCG2 knockdown SUR cells. As SCG2 was previously reported to be associated with angiogenesis, we undertook a tube formation assay. The results showed that suppression of SCG2 inhibited angiogenesis. Furthermore, coimmunoprecipitation assays revealed a direct interaction between SCG2 and hypoxia-inducible factor 1α (HIF1α). Expression levels of VEGF-A and VEGF-C downstream of HIF1α were found to be decreased in SCG2 knockdown SUR cells. In conclusion, SCG2 could be associated with sunitinib resistance through VEGF regulation in RCC cells. These findings could lead to a better understanding of the VHL/HIF/VEGF pathway and the development of new therapeutic strategies for sunitinib-resistant RCC. | |||||
| 内容記述言語 | en | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Wataru Fukumoto, Hirofumi Yoshino, Shin-Ichi Horike, Issei Kawakami, Motoki Tamai, Junya Arima, Ichiro Kawahara, Akihiko Mitsuke, Takashi Sakaguchi, Satoru Inoguchi, Makiko Meguro-Horike, Shuichi Tatarano, Hideki Enokida Potential therapeutic target secretogranin II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma Cancer Science. 2023;00:1–11. https://doi.org/10.1111/cas.15914 |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2024-02-13 | |||||
| 日付タイプ | Collected | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| ファイル（説明） | ||||||
| 内容記述 | 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 公開者・出版者 | ||||||
| 出版者 | John Wiley & Sons | |||||
| 出版者言語 | en | |||||
| 備考 | ||||||
| 備考言語 | ja | |||||
| 備考 | 【指導教員:榎田英樹】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2023-09-06 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 学位授与機関名 | 鹿児島大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2024-02-20 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲総研第724号 | |||||
