Galectin-3 Is Implicated in Tumor Progression and Resistance to Anti-androgen Drug Through Regulation of Androgen Receptor Signaling in Prostate Cancer 1

• 資料種別: 博士論文
• ISSN: 0250-7005
• タイトル: Galectin-3 Is Implicated in Tumor Progression and Resistance to Anti-androgen Drug Through Regulation of Androgen Receptor Signaling in Prostate Cancer
• 巻次・部編番号: 37 1
• 著者・編者: Dondoo, Tsogt-ochir; Fukumori, Tomoharu; Daizumoto, Kei; Fukawa, Tomoya; Kohzuki, Miho; Kowada, Minoru; Kusuhara, Yoshito; Mori, Hidehisa; Nakatsuji, Hiroyoshi; Takahashi, Masayuki; Kanayama, Hiro-omi
• 著者標目: Dondoo, Tsogt-ochir; Fukumori, Tomoharu; Daizumoto, Kei; Fukawa, Tomoya; Kohzuki, Miho; Kowada, Minoru; Kusuhara, Yoshito; Mori, Hidehisa; Nakatsuji, Hiroyoshi; Takahashi, Masayuki; Kanayama, Hiro-omi
• 出版事項: The International Institute of Anticancer Research
• 出版年月日等: 2017-01
• 出版年（W3CDTF）: 2017-01
• 並列タイトル等: ガレクチン-3は、前立腺癌におけるアンドロゲン受容体シグナル伝達の調節を介して腫瘍進展および抗アンドロゲン剤耐性に関与している; Galectin-3 in Prostate Cancer
• タイトル（掲載誌）: ANTICANCER RESEARCH
• 授与機関名: 徳島大学
• 授与年月日: 2017-02-23
• 授与年月日（W3CDTF）: 2017-02-23
• 報告番号: 甲第3011号
• 学位: 博士（医学）
• 博論授与番号: 甲第3011号
• 本文の言語コード: eng
• 件名標目: Prostate cancer; galectin-3 gene; anti-androgen resistance
• 対象利用者: 一般
• 一般注記: Background: Castration-resistant prostate cancer (CRPC)-related deaths are increasing worldwide. Therefore, clarification of the mechanisms of hormone-related tumor progression and resistance to anti-androgen drugs is useful in order to develop strategies for appropriate treatment of CRPC. Galectin-3 has been shown to be correlated with tumor progression in a variety of cancer types through the regulation of tumor proliferation, angiogenesis, and apoptosis. Materials and Methods: We examined tumor cell invasion and migration using the xCELLigence system. Control LNCaP and galectin- 3-expressing LNCaP (LNCaP-Gal-3) cells were cultured with androgen-depleted medium with 5% charcoal-stripped serum. Cells were treated for 24 h with or without dihydrotestosterone alone or combined with MDV3100 and bicalutamide; gene profile was then analyzed by microarray analysis and mRNA expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated tumor growth using spheroids and xenograft tumor growth in a mouse model. Results: In vitro, LNCaP-Gal-3 cells promoted both cell migration and invasion in an androgen-independent manner compared to control LNCaP cells. Galectin-3 also enhanced anchorage-independent growth and xenograft tumor growth even after castration. Importantly, galectin-3 greatly enhanced transcriptional activity of the androgen receptor (AR), especially on treatment with dihydrotestosterone. In microarray and qRT-PCR analyses, galectin-3 increased the expression of several AR-target genes, such as kallikreinrelated peptidase 3 (KLK3), and transmembrane protease, serine 2 (TMPRSS2). These AR-target genes were not fully suppressed by anti-androgen drugs such as bicalutamide or MDV3100. Galectin-3 significantly inhibited the effect induced by anti-androgen drugs MDV3100 and bicalutamide, suggesting that galectin-3 may be involved in resistance to anti-androgen drug through enhancement of transcriptional activity of AR and expression of AR-related genes. Conclusion: These results suggest that galectin-3 is a potential target molecule for future treatment of anti-androgen drug-resistant prostate cancer.
• DOI: info:doi/10.21873/anticanres.11297; https://doi.org/info:doi/10.21873/anticanres.11297
• 国立国会図書館永続的識別子: info:ndljp/pid/10951811; https://dl.ndl.go.jp/pid/10951811
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• 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; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2017-09-02T15:28:24+09:00
• 記録形式（IMT）: application/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
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/110097
• 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; https://dl.ndl.go.jp