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  1. C100 医学部/医学系研究科
  2. C100d 学位論文
  3. 博士論文(医保博・論医保博)

Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin

http://hdl.handle.net/2237/14839
75efa856-761f-4bfb-accc-b9ba2772395f
名前 / ファイル ライセンス アクション
k9069.pdf k9069.pdf (1.3 MB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2011-05-20
タイトル
タイトル Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin
その他のタイトル
その他のタイトル ヒト乳癌細胞株MCF-7 における抗癌剤ダウノルビシン による中性スフィンゴミエリナー2 遺伝子発現の転写調節機序
著者 伊藤, 裕美

× 伊藤, 裕美

WEKO 40803

伊藤, 裕美

Search repository
キーワード
主題Scheme Other
主題 NSMase2
キーワード
主題Scheme Other
主題 Daunorubicin
キーワード
主題Scheme Other
主題 Ceramide
キーワード
主題Scheme Other
主題 Promoter analysis
キーワード
主題Scheme Other
主題 EMSA
キーワード
主題Scheme Other
主題 ChIP
キーワード
主題Scheme Other
主題 Sp family protein
抄録
内容記述 Mg^2+-dependent neutral SMases (NSMases) have emerged as prime candidates for stress-induced ceramide production. Among isoforms identified, previous reports have suggested the importance of NSMase2. However, its activation mechanism has not been precisely reported. Here, we analyzed the mechanism of NSMase2 gene expression by the anti-cancer drug, daunorubicin (DA). DA increased cellular ceramides (C16, C18 and C24) and NSMase activity of a human breast cancer cell line, MCF-7. DA remarkably increased the NSMase2 message and protein, whereas little change in NSMase1 and NSMase3 mRNA and only a mild increase in acid SMase mRNA were observed. Overexpression and a knock down of NSMase2 indicated that NSMase2 played a role in DA-induced cell death. NSMase2 promoter analysis revealed that three Sp1 motifs located between -148~-42 bp upstream of the first exon were important in basic as well as in DA-induced promoter activity. Consistently, luciferase vectors containing three consensus Sp1-motifs but not its mutated form showed DA-induced transcriptional activation. DA-treated MCF-7 showed increased Sp3 protein. In SL2 cells lacking Sp family proteins, both Sp1 and Sp3 overexpression increased NSMase promoter activity. Increased binding of Sp family proteins by DA to three Sp1 motifs was shown by electrophoresis mobility-shift and ChIP assays.
内容記述タイプ Abstract
内容記述
内容記述 名古屋大学博士学位論文 学位の種類:博士(医療技術学) (課程) 学位授与年月日:平成23年3月25日
内容記述タイプ Other
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_46ec
タイプ thesis
書誌情報 発行日 2011-03-25
学位授与年度
学位授与年度 2010
学位授与年月日
学位授与年月日 2011-03-25
学位授与番号
学位授与番号 13901甲第9069号
著者版フラグ
値 publisher
URI
識別子 http://hdl.handle.net/2237/14839
識別子タイプ HDL
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