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.
Masuoka
J
J
Department of Neurosurgery, Saga Medical School, Saga 849-8501, Japan.
Shiraishi
T
T
Ichinose
M
M
Mineta
T
T
Tabuchi
K
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D051017:Apoptosis Regulatory Proteins; D020033:Protein Isoforms; D011506:Proteins; C411023:anti-Fas monoclonal antibody; C109664:caspase-activated DNase inhibitor; D019014:fas Receptor