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

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Kyoto Prefectural University medicine
• Principal Investigator: SUGAWA Noriaki Kyoto Prefectural University medicine Medical school, assistant Professor, 医学部, 助手 (50244596)
• Co-Investigator(Kenkyū-buntansha): KITA Masakazu Kyoto Prefectural University medicine Medical school, associate Professor, 医学部, 助教授 (60153087)
• Project Period (FY): 1999 – 2001
• Keywords: malignant glioma / apoptosis / gene therapy / p53 / p130

Research Abstract

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.