Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

• Material Type: 博士論文
• ISSN: 1471-2407
• Title: Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer
• Volume: 16
• Author/Editor: 富永, 哲郎
• Author Heading: 富永, 哲郎
• Publication, Distribution, etc.: BioMed Central
• Publication Date: 2016-09-07
• Publication Date (W3CDTF): 2016-09-07
• Alternative Title: 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
• Periodical title: BMC Cancer
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2016-09-07
• Date Granted (W3CDTF): 2016-09-07
• Dissertation Number: 甲医歯薬第886号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医歯薬第886号
• Text Language Code: eng
• Subject Heading: Non-small-cell lung cancer; Sp1; Dihydropyrimidine dehydrogenase; Epidermal growth factor receptor mutation; 5-fluorouracil
• Target Audience: 一般
• Note (General): 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. AmongEGFR-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.; 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; Author: Tetsuro Tominaga, Tomoshi Tsuchiya, Koji Mochinaga, Junichi Arai, Naoya Yamasaki, Keitaro Matsumoto, Takuro Miyazaki, Toshiya Nagasaki, Atsushi Nanashima, Kazuhiro Tsukamoto, Takeshi Nagayasu; Citation: BMC Cancer, 16, 354; 2016; Nagasaki University (長崎大学), 博士(医学) (2016-09-07)
• DOI: info:doi/10.1186/s12885-016-2392-0; https://doi.org/info:doi/10.1186/s12885-016-2392-0
• Persistent ID (NDL): info:ndljp/pid/10200789; https://dl.ndl.go.jp/pid/10200789
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2016-10-01T18:16:16+09:00
• Date Created (W3CDTF): 2020-12-21
• Format (IMT): PDF
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10069/36831; https://nagasaki-u.repo.nii.ac.jp/records/3657
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

Table of Contents

2021-03-07 再収集