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博士論文
国立国会図書館館内限定公開
収録元データベースで確認する
国立国会図書館デジタルコレクション
デジタルデータあり(鹿児島大学)
T-box転写因子BRACHYURYと転写因子SOX2は腺様嚢胞癌の自己再生能と浸潤能を亢進する : 新規治療法創出の可能性
- 国立国会図書館永続的識別子
- info:ndljp/pid/11279024
- 資料種別
- 博士論文
- 著者
- 中村, 康大
- 出版者
- 鹿児島大学
- 出版年
- 2019-03-25
- 資料形態
- デジタル
- ページ数・大きさ等
- -
- 授与大学名・学位
- 鹿児島大学,博士(歯学),Doctor of Philosophy in Dental Science
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- 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Background: The high frequencies of recurrence and distant metastasis of adenoid cystic carcinoma (ACC) emphasize th...
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デジタル
- 資料種別
- 博士論文
- 著者・編者
- 中村, 康大
- 著者標目
- 出版事項
- 出版年月日等
- 2019-03-25
- 出版年(W3CDTF)
- 2019-03-25
- 並列タイトル等
- T-box Transcription Factor BRACHYURY and SOX2 Increase Self-Renewal and Invasive Phenotype in Adenoid Cystic Carcinoma : Implication for a New Therapeutic Principle
- 授与機関名
- 鹿児島大学
- 授与年月日
- 2019-03-25
- 授与年月日(W3CDTF)
- 2019-03-25
- 報告番号
- 甲総研第505号
- 学位
- 博士(歯学)Doctor of Philosophy in Dental Science
- 博論授与番号
- 甲総研第505号
- 本文の言語コード
- eng
- 件名標目
- NDC
- 対象利用者
- 一般
- 一般注記
- 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Background: The high frequencies of recurrence and distant metastasis of adenoid cystic carcinoma (ACC) emphasize the need to better understand the biological factors associated with these outcomes. Recent studies suggest that epithelial–mesenchymal transition (EMT) correlates with cancer metastasis. In addition, there is growing evidence of the association of EMT with cancer stem cells (CSCs). Recently, we showed that the T-box transcription factor BRACHYURY could be a strong regulator of EMT. Further, we previously established the metastatic ACCS-M GFP cell line and reported that SOX2 knockdown partially inhibits EMT phenotypes of ACCS-M GFP cells. Thus, in this study, we further tested whether BRACHYURY and SOX2 is a regulator of cancer stemness by means of forced expression and silencing of these genes in adenoid cystic carcinoma (ACC) cell lines.Methods: BRACHYURY, SOX2, or both were transfected into ACC cell lines. Short hairpin RNA (shRNA) silencing of these genes was also performed. We analysed these cell lines with respect to self-renewal phenotypes using a sphere-formation assay, and we assessed the expression levels of EMT markers and stem cell markers using real-time reverse transcription-polymerase chain reaction (RT-PCR). Cell migration and invasiveness in vitro were evaluated using a wound healing assay and a tumor cell dissemination assay, respectively. Characteristics of CSCs were also analyzed by sphere-forming ability and in vivo tumorigenicity.Results: Forced expression of BRACHYURY or SOX2 slightly increased expression of EMT and stem cell markers and the self-renewal phenotype. The expression levels, however, were much lower compared to those of cancer stem cell-like cells. Forced co-expression of BRACHYURY and SOX2 strongly upregulated EMT and stem cell markers and the self-renewal phenotype. Cell migration and invasiveness in vitro were also remarkably enhanced. These synergistic effects increased expression levels of FIBRONECTIN, SNAIL, SLUG, ZEB1, and TGF-β2. In particular, the effects on FIBRONECTIN and TGF-β2 were significant. BRACHYURY knockdown significantly inhibited cell migration and invasion, and decreased tumorigenicity in ACC cells.Conclusions: We found that BRACHYURY and SOX2 synergistically promote cancer stemness in ACC cells. This finding points to the importance of gene or protein networks associated with BRACHYURY and SOX2 in the development and maintenance of the CSC phenotype. This study demonstrates that BRACHYURY knockdown reduces invasiveness of CSCs in vivo, suggesting that BRACHYURY silencing may be a useful therapeutic tool for salivary gland carcinoma including adenoid cystic carcinoma.The part of this thesis is originally based on:Naonari Akimoto, Kodai Nakamura, Hiroshi Hijioka, Kenichi Kume, Yoshiaki Matsumura and Tsuyoshi SugiuraTransfection of T-Box Transcription Factor BRACHYURY and SOX2 Synergistically Promote Self-Renewal and Invasive Phenotype in Oral Cancer CellsInternational Journal of Molecular Sciences 2018, 19(11):3620DOI: 10.3390/ijms19113620
- 国立国会図書館永続的識別子
- info:ndljp/pid/11279024
- コレクション(共通)
- コレクション(障害者向け資料:レベル1)
- コレクション(個別)
- 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
- 収集根拠
- 博士論文(自動収集)
- 受理日(W3CDTF)
- 2019-05-06T10:27:56+09:00
- 作成日(W3CDTF)
- 2019-04-19
- 記録形式(IMT)
- PDFapplication/pdf
- オンライン閲覧公開範囲
- 国立国会図書館内限定公開
- デジタル化資料送信
- 図書館・個人送信対象外
- 遠隔複写可否(NDL)
- 可
- 連携機関・データベース
- 国立国会図書館 : 国立国会図書館デジタルコレクション