Expression of ICAD-l and ICAD-S in human brain tumor and its cleavage upon activation of apoptosis by anti-Fas antibody.

ICAD / DFF is a downstream molecule of caspases, participating in nuclear DNA fragmentation during apoptosis. ICAD / DFF binds CAD / DFF40 and inhibits its DNase activity. ICAD / DFF has two alternative isoforms, long isoform (ICAD-L / DFF45) and short isoform (ICAD-S / DFF35). We have studied the presence and functional status of ICAD / DFF in human glioma cell lines. All cell lines tested expressed both ICAD-L and ICAD-S. When the cultured glioma cells were exposed to anti-Fas antibody, these isoforms were degraded prior to the fragmentation of the nuclear DNA, indicating that the ICAD / DFF expressed in cultured glioma cells was potentially functional. In primary brain tumors and normal brain tissues, there was a difference in the expression level between ICAD-L and ICAD-S. In glioblastomas, ICAD-S was more abundant than ICAD-L. In contrast, ICAD-L was more abundant than ICAD-S in medulloblastomas. The present findings suggest that primary brain tumors and normal brain constitutively express ICAD / DFF, and that there is a difference between the expression levels of ICAD-L and ICAD-S.