The involvement of sphingolipid metabolism in anti cancer drug sensitivity of malignant cells

鞘脂代谢参与恶性细胞抗癌药物敏感性

• 批准号: 23590667
• 负责人: MURATE Takashi
• 金额: $ 3.49万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590667/
• 关键词: sphingolipid; metabolic enzyme; gene expression; anti-cancer drug; human cancer cell lines; SPHK1; Friend cell; c-Myb; chemical differentiation; human colon cancer cell; CD44; S1P receptor 2; ERK pathway; 国際情報交換; NSmase2; ATRA; MCF-7細胞株

In the first year, we analyzed the mechanism of GAP43 expression during GDNF treatment of a neuronal cel line, TGW. Our analysis revealed that GDNF induced SPHK1 expression through RET receptor, followed by S1P secretion and S1P1/3 receptor activation. We further found that GAP43 expression was due to the increased CREB transcription factor binding to the GAP43 5'-promoter region.Next, we analyzed the regulatory mechanism of neutral sphingomyelinase 2 and neutral ceramidase with all trans retinoid acid (ATRA). Our analysis revealed that activated Sp1 transcription factor and decreased GATA2 were responsive for the observed changes in treated MCF-7 and SH-SY5Y cells, respectively.In the third year, we analyzed the mechanism of high SPHK1 expression of mouse Friend cells. We found that c-MYB is responsible for this overepression and that chemical inducer, HMBA, rapidly decreased SPHK1 expression, which is at least partially responsible for this terminal differentiation process.

在第一年，我们分析了GDNF处理神经元细胞系TGW期间GAP 43表达的机制。我们的分析显示GDNF通过RET受体诱导SPHK 1表达，随后是S1 P分泌和S1 P1/3受体激活。我们进一步发现GAP 43的表达是由于CREB转录因子与GAP 43 5 '-启动子区域结合增加所致。我们的分析表明，激活的Sp1转录因子和减少的GATA 2分别对处理后的MCF-7和SH-SY 5 Y细胞中观察到的变化作出反应。我们发现，c-MYB是负责这种抑制和化学诱导剂，HMBA，迅速降低SPHK 1的表达，这是至少部分负责这个终端分化过程。

项目成果

Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB.

由于 c-MYB 减少，鞘氨醇激酶 1 表达在 Friend 细胞分化过程中下调。

• DOI: 10.1016/j.bbamcr.2013.01.001
• 发表时间: 2013
• 期刊: Biochimica et Biophysica Acta -Molecular Cell Research
• 作者: Mizutani N;Kobayashi M;Sobue S;Ichihara M;Ito H;Tanaka K;Iwaki S,Fujii S,Ito Y;Tamiya-Koizumi K;Takagi A;Kojima T;Naoe T;Suzuki M;Nakamura M;Banno Y;Nozawa Y;Murate T.
• 通讯作者: Murate T.

アンドロジェン反応性ヒト前立腺がん細胞株LNCaPにおける酸性セラミダーゼ発現調節機序

雄激素反应性人前列腺癌细胞系LNCaP中酸性神经酰胺酶表达的调控机制

• 发表时间: 2012
• 作者: 東田修二;大野彩;高橋祐介;奥橋佑基;伊藤真以;Toru Takano;登勉;井上みなみら
• 通讯作者: 井上みなみら

Hybrid liposomes affect cellular lipids

混合脂质体影响细胞脂质

• 发表时间: 2012
• 期刊: Bioorg Med Chem Lett
• 影响因子: 2.7
• 作者: Hiroyuki Yasui;Yutaro Natsume;and Yutaka Yoshikawa;Cao K. et al.
• 通讯作者: Cao K. et al.

C-Myb is the major regulator of sphingosine kinase 1 expression of Friend cells

C-Myb 是 Friend 细胞鞘氨醇激酶 1 表达的主要调节因子

• 发表时间: 2012
• 作者: Ohyama Yoshiaki;Kurabayashi Masahiko;Mizutani N. et al.
• 通讯作者: Mizutani N. et al.

Sphk 1 of Friend cells was decreased by HMBA

HMBA 降低 Friend 细胞的 Sphk 1

• 作者: Yamada;H.;Takano;T.;Kihara;M.;Hirokaw,a M.;Yoshida;H.;Watanabe;M.;Iwatani;Y.;Hidaka;Y.;.Miyauchi;A;小林 美沙ら
• 通讯作者: 小林 美沙ら