STUDY OF MECHANISMS OF DIFFERENTIATION AND RESISTANCE TO ANTI-CANCER AGENT OF EMBRYONAL CARCINOMA CELLS

胚胎癌细胞分化及抗癌药物抵抗机制的研究

• 批准号: 09672046
• 负责人: MORITA Takashi
• 金额: $ 1.98万
• 依托单位: OSAKA CITY UNIVERSITY MEDICAL SCHOOL (1998)Osaka University (1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672046/
• 关键词: embryonal carcinoma cell; cisplatin; apoptosis; cell cycle; RecA; Rad51; antisense DNA; 抗癌剤耐性; p53; DNA修復; 分化; 相同組み換え

(1) We demonstrated that cisplatin induced growth suppression followed by induction of differentiation in teratocarcinoma F9 cells. In this study, we investigated the mechanism of the effect of cisplatin for cell cycle progression in F9 cells focusing on the change of p34^<cdc2>. By the treatment, the level of the expressionof cdc2 mRNA did not change, but the half life of p34^<cdc2> was greatly reduced, which would result in the arrest the cell cycle at the late S to G2/M.(2) The mammalian Rad51 gene is a homolog of the yeast Rad5l and E.coli RecA genes, which are related to the repair of DNA double-strand breaks and are also involved in recombination repair and various SOS responses to DNA damage by g-irradiation and alkylating agent like anticancer agent. In this study, we demonstrated that Rad51 antisense oligonucleotides enhances the radiosensityivity of mouse malignant gliomas in vivo and in vitro, suggesting the potentiation for radiation therapy in malignant gliomas by inhibiting DNA double-strand break repair.

(1)我们证实了顺铂对畸胎癌F9细胞的生长抑制和诱导分化作用。本研究旨在探讨顺铂对F9细胞周期进程的影响机制，重点探讨顺铂对F9细胞p34、lt、cdc2、gt；经处理后，cdc2mRNA的表达水平没有改变，但p34^-lt；cdc2-gt的半衰期大大缩短，导致细胞周期停滞于S晚期至G2/M期。(2)哺乳动物的RAD51基因是酵母RAD51和E.ColiRecA基因的同源基因，与DNA双链断裂的修复有关，也参与重组修复和多种SOS反应，以应对g-射线和烷化剂类抗癌药物对DNA损伤的损伤。在本研究中，我们证明了RAD51反义寡核苷酸在体内和体外都增强了小鼠恶性胶质瘤的放射敏感性，提示通过抑制DNA双链断裂修复来增强恶性胶质瘤的放射治疗。

项目成果

Yoshida K.et al: "The Mouse RecA-like Gene,DmcI is required for recognition of homologs in meiotic synapssis." Mol Cell. (in press). (1998)

Yoshida K.等人：“小鼠 RecA 样基因 DmcI 是减数分裂突触中同系物识别所必需的。”

Yosida,et al.: "The Mouse RecA-like Gene,Dmcl is required for homologous chromosome synapsis during meiosis." Mol.Cell. 1. 707-718 (1998)

Yosida 等人：“减数分裂过程中同源染色体突触需要小鼠 RecA 样基因 Dmcl。”

Ohnishi,T.et al.: "In Vitro and in Vivo Potentiation of Radiosensitivity of Malignant Gliomas by Antisense Inhibition of the RAD51 Gene." Biochem.Biophys.Res.Commun.245. 319-324 (1998)

Ohnishi,T.et al.：“通过反义抑制 RAD51 基因在体外和体内增强恶性神经胶质瘤的放射敏感性。”

Yoshida, K., Kondoh, G., Matsuda, Y., Habu, T., Nishimune, T., Morita, T.: "The mouse RecA-like Gene, Dmcl is required for homologous chromosome synapsis during meiosis." Mol.Cell. 1. 707-718 (1998)

Yoshida, K.、Kondoh, G.、Matsuda, Y.、Habu, T.、Nishimune, T.、Morita, T.：“小鼠 RecA 样基因 Dmcl 是减数分裂过程中同源染色体突触所必需的。”

Ohnishi,T.et al.: "In Vitro and in Vivo Potentiation of Radiosensitivity of Malignant Gliomas by Antisense Inhibition of the RAD51 Gene." Biochem. Biophys.Res.Commun.245. 319-324 (1998)

Ohnishi,T.et al.：“通过反义抑制 RAD51 基因在体外和体内增强恶性神经胶质瘤的放射敏感性。”