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Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer
http://hdl.handle.net/10069/36831
http://hdl.handle.net/10069/36831f1204cab-d62c-4158-a6fc-4a237da524ee
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ISYK886_Tominaga.pdf (1.6 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2016-09-13 | |||||
| タイトル | ||||||
| タイトル | Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Non-small-cell lung cancer | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Sp1 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Dihydropyrimidine dehydrogenase | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Epidermal growth factor receptor mutation | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | 5-fluorouracil | |||||
| 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 | |||||
| 著者 |
富永, 哲郎
× 富永, 哲郎 |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 115430 | |||||
| 姓名 | Tominaga, Tetsuro | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background: It has been shown that epidermal growth factor receptor (EGFR) mutation status is associated with 5-fluorouracil (5-FU) sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR mutation status and dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, is unknown. Methods: We elucidated the crosstalk among the EGFR signal cascade, the DPD gene (DPYD), and DPD protein expression via the transcription factor Sp1 and the effect of EGFR mutation status on the crosstalk. Results: In the PC9 (exon19 E746-A750) study, EGF treatment induced up-regulation of both Sp1 and DPD; gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), and mithramycin A, a specific Sp-1 inhibitor, suppressed them. Among EGFR-mutated (PC9, HCC827; exon19 E746-A750 and H1975; exon21 L858R, T790M, gefitinib resistant) and -non-mutated (H1437, H1299) cell lines, EGF administration increased DPYD mRNA expression only in mutated cells (p < 0.05). Accordingly, gefitinib inhibited DPD protein expression only in PC9 and HCC827 cells, and mithramycin A inhibited it in EGFR-mutated cell lines, but not in wild-type. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line. Conclusions: The EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status. |
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| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第886号 学位授与年月日:平成28年9月7日 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Author: Tetsuro Tominaga, Tomoshi Tsuchiya, Koji Mochinaga, Junichi Arai, Naoya Yamasaki, Keitaro Matsumoto, Takuro Miyazaki, Toshiya Nagasaki, Atsushi Nanashima, Kazuhiro Tsukamoto, Takeshi Nagayasu | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: BMC Cancer, 16, 354; 2016 | |||||
| 書誌情報 |
BMC Cancer 巻 16, p. 354, 発行日 2016-09-07 |
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| EISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 14712407 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1186/s12885-016-2392-0 | |||||
| 権利 | ||||||
| 権利情報 | c 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| その他のタイトル | ||||||
| その他のタイトル | EGFR変異型非小細胞肺癌におけるEGFシグナルのDPD発現調整 | |||||
| 出版者 | ||||||
| 出版者 | BioMed Central | |||||
| 学位名 | ||||||
| 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 | 17301 | |||||
| 学位授与機関名 | Nagasaki University (長崎大学) | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2016-09-07 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲医歯薬第886号 | |||||
| 学位の種類 | ||||||
| 値 | 課程博士 | |||||
| 引用 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Nagasaki University (長崎大学), 博士(医学) (2016-09-07) | |||||
