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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)

Sphingosine kinase 1 expression is involved in leukemogenesis and modulates cellular sphingolipid rheostat, which is a good predictive marker of daunorubicin sensitivity

http://hdl.handle.net/2237/9693
http://hdl.handle.net/2237/9693
0abaeef0-2bb8-4c20-a01a-c4d098a60e97
名前 / ファイル ライセンス アクション
k7769_thesis.pdf k7769_thesis.pdf (461.2 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2008-04-18
タイトル
タイトル Sphingosine kinase 1 expression is involved in leukemogenesis and modulates cellular sphingolipid rheostat, which is a good predictive marker of daunorubicin sensitivity
言語 en
著者 祖父江, 沙矢加

× 祖父江, 沙矢加

WEKO 22710

ja 祖父江, 沙矢加

Search repository
SOBUE, Sayaka

× SOBUE, Sayaka

WEKO 22711

en SOBUE, Sayaka

Search repository
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
キーワード
主題Scheme Other
主題 Sphingolipid metabolic enzyme
キーワード
主題Scheme Other
主題 Sphingosine kinase 1
キーワード
主題Scheme Other
主題 Neutral sphingomyelinase 2
キーワード
主題Scheme Other
主題 quantitative RT-PCR
キーワード
主題Scheme Other
主題 Daunorubicin
キーワード
主題Scheme Other
主題 Chemosensitivity
キーワード
主題Scheme Other
主題 Ceramide
キーワード
主題Scheme Other
主題 Sphingosine 1-phosphate
抄録
内容記述 It was reported that sphingosine kinase (SPHK) gene expression was increased in tumor tissues and that overexpression of SPHK1 in solid tumor cell lines was involved in anti-cancer drug resistance. Here, we reported the increase in sphingosine kinase 1 (SPHK1) and decrease in neutral sphingomyelinase 2 (NSMase2) gene expression in myelodysplastic syndromes and acute leukemia. This alteration is supposed to change the cellular sphingolipid rheostat and effects anti-cancer drug sensitivity. However, positive correlations were observed between daunorubicin (DA)-IC_50 and the SPHK1 message but not between DA-IC_50 and NSMase2 messages, when 16 different leukemia cell lines were used to analyze the relationship between gene expressions and the chemosensitivity against DA. Using two cell lines with either the highest or the lowest SPHK1 expression, cellular ceramides and sphingosine 1-phosphate (S1P) were quantified by liquid chromatography/mass spectrometry. Increased ceramide was observed in DA-sensitive, but not in DA-resistant cell lines treated with low doses of DA. Upon DA treatment, S1P decreased more in the sensitive cell line than in the resistant cell lines. A SPHK inhibitor recovered the DA-sensitivity of DA-resistant cells. Furthermore, the modulation of SPHK1 gene expression by either overexpression or using siRNA affected the DA sensitivity of representative cell lines. Our results clearly show that the sphingolipid rheostat plays a significant role in DA-induced cytotoxicity of leukemia cells, and suggest that SPHK1 is both a good marker to predict DA-sensitivity of leukemia cells and a potential therapeutic target for leukemia with high SPHK1 expression.
言語 en
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20年3月25日
言語 ja
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_db06
タイプ doctoral thesis
書誌情報
発行日 2008-03-25
学位名
言語 ja
学位名 博士(医療技術学)
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 13901
言語 ja
学位授与機関名 名古屋大学
言語 en
学位授与機関名 NAGOYA University
学位授与年度
学位授与年度 2007
学位授与年月日
学位授与年月日 2008-03-25
学位授与番号
学位授与番号 甲第7769号
フォーマット
application/pdf
著者版フラグ
値 publisher
URI
識別子 http://hdl.handle.net/2237/9693
識別子タイプ HDL
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