Vaccination therapy against malignant glioma using apoptosis-inducing genes

点击翻译按钮获取中文摘要

We cloned several genes whose expression level increase or decrease along with the progression of myc-induced apoptosis in glioma cells by differential display PCR method. One of the genes was calmodulin. Therefore, in this study, we hypothesized that calciummediated signal transduction may be involved in apoptosis and the activation of immunogenicity in malignant glioma cells and tried to investigate their molecular mechanism by confirming the hypothesis. Although we have not reached the final goal, we have found the following several important findingsregarding molecular mechanisms of apoptosis : (1) the expression level of calcineurin is extremely high in the brain as was reported ; (2)when the activity of calcineurin increases, the activity of proteasome decreases ; (3)when the proteasome activity was perturbed by inhibitors, apoptosis is induced in the cells ; (4)as a result, the cells with high calcineurin activity are vulnerable to apoptosis. These results may elucidate that hippocampal CA1 neurons with high calcineurin expression are vulnerable to delayd neuronal death induced by transient iscemia although these results are not exclusive to neural cells. It is probable that gliomaspecific mechanisms such as sctivation of tumor-immunogenicity are located downstream of the proteasome function. It is extremely important to clarify the function of proteasome in apoptosis and activation of tumor-immunogenicity and such a project is in progress.