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) 我们证明顺铂诱导生长抑制，随后诱导畸胎癌 F9 细胞分化。在本研究中，我们研究了顺铂对F9细胞细胞周期进展的影响机制，重点关注p34^<cdc2>的变化。经处理后，cdc2 mRNA的表达水平没有变化，但p34^<cdc2>的半衰期大大缩短，导致细胞周期停滞在S晚期至G2/M。(2)哺乳动物Rad51基因是酵母Rad5l和大肠杆菌RecA基因的同源物，与DNA双链断裂的修复有关，也参与重组修复和对DNA的各种SOS反应g-辐射和烷化剂（如抗癌剂）造成的损伤。在这项研究中，我们证明Rad51反义寡核苷酸在体内和体外增强小鼠恶性神经胶质瘤的放射敏感性，表明通过抑制DNA双链断裂修复来增强恶性神经胶质瘤的放射治疗。

项目成果

Tsuzuki, T.Fujii, Y., Sakumi, K., Tominaga, Y., Nakao, K., Sekiguchi, M., Matsushiro, A., Yoshimura, Y., Morita, T.: "Targeted disruption of the Rad51 gene leads to lethality in embryonic mice." Proc.Natl.Acad.Sci.USA. 93. 6236-6240 (1996)

Tsuzuki, T.Fujii, Y.、Sakumi, K.、Tominaga, Y.、Nakao, K.、Sekiguchi, M.、Matsushiro, A.、Yoshimura, Y.、Morita, T.：“Rad51 的定向破坏

Yamamoto,A.et al.: "Cell cycle-dependent expression of the mouse Rad51 gene in proliferating cells." Mol.Gen.Genet. 251. 1-12 (1996)

Yamamoto,A.et al.：“增殖细胞中小鼠 Rad51 基因的细胞周期依赖性表达。”

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。”

Taki, T., Ohnishi, T., Yamamoto, A, Mori, K., Iwaisako, K., Hiraga, S., Arita, N., Izumoto, S., Hayakawa, T., Morita, T.: "Antisense inhibition of the RAD51 enhances radiosensitivity." Biochem.Biophys.Res.Commun.223. 434-438 (1996)

泷，T.，大西，T.，山本，A，森，K.，岩佐子，K.，平贺，S.，有田，N.，泉本，S.，早川，T.，森田，T.：“

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

Yoshida 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。”