Analysis of apoptotic related gene in malignant glioma and development of the gene therapy

恶性胶质瘤细胞凋亡相关基因分析及基因治疗进展

• 批准号: 11671376
• 负责人: SOGAWA Noriaki
• 金额: $ 2.24万
• 依托单位: Kyoto Prefectural University medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671376/
• 关键词: malignant glioma; apoptosis; gene therapy; p53; p130; malignant glioma; gene therapy; EGFR

From the analysis of Apoptosis relation gene (bax, bcl-2, bcl-xl), it was discovered that the expression of abnormal EGFR was related to the expression of bcl-xl. The result using these experimental models got the similar result from the research using our operation cases. The tumor proliferation capability (the MIB-1 positive rate) was high in malignant glioma over expressing abnormal EGFR, and it was clinically discovered that it tended to suppress apoptosis and tended to also over express bcl-XL. However, there were the cases in which apoptosis occurred in spite of over expression of bcl-xl in the operation cases. In such case, the expression of bax has been recognized. The appearance of apoptosis was related to the ratio of bax/bcl-XL in malignant glioma. Bcl-XL in apoptosis of malignant glioma, it was made to be an inhibitor, and bax was related as an induction gene. It was found that abnormal EGFR was related the expression of bcl-XL. We analyzed the expression of bax and mutation type of p53 in the sixty operation cases. In the result, there was a tendency of the way which anticipated the relationship between p53 and bax. In short, wild type p53 makes the bax expression promote, and mutant type p53 does suppress the bax expression. Then, we insert exogenous p53 gene or p130 gene in four kinds of gene recombination cell line. Then, we examined the expression of p53 family and bax in vitro. However, we could not have the results of the relationship between p53 family and bax, which we expected. From these results, we could estimate that p53 family send a signal via a new gene to bax. But, we could not determine this new gene.

通过对凋亡相关基因（bax、bcl-2、bcl-xl）的分析，发现异常EGFR的表达与bcl-xl的表达有关。利用这些实验模型得到的结果与实际操作案例的研究结果相似。过表达异常EGFR的恶性胶质瘤具有较高的肿瘤增殖能力（mb -1阳性率），临床发现其有抑制细胞凋亡的倾向，也有过表达bcl-XL的倾向。然而，在手术病例中，尽管bcl-xl过表达，但仍有发生细胞凋亡的情况。在这种情况下，bax的表达已被识别。恶性胶质瘤细胞凋亡的发生与bax/bcl-XL比值有关。Bcl-XL在恶性胶质瘤细胞凋亡中起抑制作用，bax作为诱导基因相关。发现EGFR异常与bcl-XL的表达有关。我们分析了60例手术病例中bax的表达和p53的突变类型。结果表明，p53与bax之间的关系有预测的趋势。总之，野生型p53促进bax的表达，突变型p53抑制bax的表达。然后，我们将外源p53基因或p130基因插入四种基因重组细胞系中。然后，我们在体外检测p53家族和bax的表达。然而p53家族与bax之间的关系，我们并没有得到我们预期的结果。根据这些结果，我们可以估计p53家族通过一个新基因向bax发送信号。但是，我们无法确定这个新基因。