Clarification of response mechanism in U937 cells against heat treatment

阐明U937细胞对热处理的反应机制

• 批准号: 14370271
• 负责人: SUZUKI Norio
• 金额: $ 8.19万
• 依托单位: International University of Health and Welfare (2003)The University of Tokyo (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370271/
• 关键词: SAPK; JNK; wortmannin; hyperthermia; cell death; apoptosis; DNA-PK; Heat sensitization; U937 cells; p53; 温熱; シグナル伝達; p53 null; U937細胞; 細胞死、アポトーシス; 温熱高感受性; Akt; Wortmannin; リン酸化特異抗体; 細胞死; セラミド; 温熱療法

The overall goal of the present project has been to analyze mechanisms of heat-induced apoptotic cell death and radio-sensitization for better treatment of cancer. Toward this goal, we have accomplished the following progress.1)We have clarified the involvement of ceramide-SAP/JNK pathway, and radio-sensitization process in heat-induced apoptotic cell death.2)RT-PCR analysis of apoptosis-related genes revealed that the expression of c-myc gene was reduced in the process of cell death. The introduction of c-myc antisense oligonucleotides or the treatment of c-Myc inhibitor induced cell death.3)Involvement and the role of DNA-PK in radio-sensitization by heat was evaluated using various repair deficient and knockout mutants of mammalian cells and DT40 chicken cells.4)We found appearance of fragment of JNK, which were identified as cleaved products by Caspase 3 from INK.

本项目的总体目标是分析热诱导细胞凋亡和放射增敏的机制，以更好地治疗癌症。为此，我们取得了以下进展：1)阐明了神经酰胺-SAP/JNK通路和辐射增敏过程在热诱导细胞死亡中的作用。2)RT-PCR分析表明，c-myc基因在细胞死亡过程中表达下调。C-myc反义寡核苷酸的引入或c-Myc抑制剂的处理诱导了细胞死亡。3)利用哺乳动物细胞和DT40细胞的各种修复缺陷和敲除突变体，研究了DNA-PK的参与及其在辐射热敏化中的作用。4)我们发现了JNK片段的出现，经Caspase 3鉴定为墨汁中的切割产物。

项目成果

Tomita, M., Suzuki, N., Matsumoto, Y., Enomoto, A., Yin, H.-L., Hosoi, Y., Hirano, K., Sakai, K.: "Wortmannin-enhanced X-ray-induced apoptosis of human T-cell leukemia MOLT-A cells possibly through the JNK/SAPK pathway."Radiat.Res.. 160. 467-477 (2003)

Tomita, M.、Suzuki, N.、Matsumoto, Y.、Enomoto, A.、Yin, H.-L.、Hosoi, Y.、Hirano, K.、Sakai, K.：“渥曼青增强 X 射线

Hosoi, Y., Matsurnoto, Y., Tomita, M., Enomoto, A., Morita, A., Sakai, K., Nakagawa, K., Umeda, N., Zhao, H, -J., Ono, T., Suzuki, N.: "Phosphorothioate oligonucleotides, suramin and heparin inhibit DNA-dependent protein kinase activity."Brit.J.Cancer. 86

细井 Y.、松能登 Y.、富田 M.、榎本 A.、森田 A.、酒井 K.、中川 K.、梅田 N.、赵 H、-J.、小野，

Komuro, Y., Watanabe, T., Hosoi, Y., Matsumoto, Y., Nakagawa, K., Kitayama, J., Suzuki, N., Nagawa, H.: "The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma."Cancer. 95. 1195-1205

Komuro, Y.、Watanabe, T.、Hosoi, Y.、Matsumoto, Y.、Nakakawa, K.、Kitayama, J.、Suzuki, N.、Nagawa, H.：“Ku 的表达模式与肿瘤放射敏感性相关

Enomoto, A., Suzuki, N., Kang, Y., Hirano, K., Matsumoto, Y., Zhu, J., Morita, A., Hosoi, Y., Sakai, K., Koyama, H.: "Decreased c-Myc expression and its involvement in X-ray-induced apoptotic cell death of human T-cell leukemia cell line MOLT-4."Int.J.Rad

Enomoto, A.、Suzuki, N.、Kang, Y.、Hirano, K.、Matsumoto, Y.、Zhu, J.、Morita, A.、Hosoi, Y.、Sakai, K.、Koyama, H.：

Komuro, Y., et al.: "The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma."Cancer. 95. 1195-1205 (2002)

Komuro, Y. 等人：“Ku 的表达模式与直肠癌患者的肿瘤放射敏感性和无病生存期相关。”癌症。