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Int J Cancer. 2010 Apr 15;126(8):1982-1991. doi: 10.1002/ijc.24965.

Sterile alpha motif containing domain 9 is involved in death signaling of malignant glioma treated with inactivated Sendai virus particle (HVJ-E) or type I interferon.

Author information

1
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
2
Department of Neurosurgery, Tokyo Women's Medical University, Kawadachou, Shinjuku-ku, Tokyo, Japan.
3
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Abstract

Malignant glioma is one of the most aggressive cancers. For the development of effective therapeutic strategies against such malignant diseases, elucidation of molecular targets is necessary. We found that inactivated Sendai virus particle (HVJ-E) induced extensive cell death in the human glioblastoma cell line U251MG. Intradermal U251MG tumors were more effectively suppressed by HVJ-E than interferon (IFN)-beta. From microarray analysis of gene expression in U251MG cells treated with HVJ-E, we focused on the up-regulation of sterile alpha motif containing domain 9 (SAMD9) gene. The expression of the SAMD9 gene was induced by administration of recombinant human IFN-alpha, -beta or -gamma. The up-regulation of the SAMD9 gene by HVJ-E treatment was abrogated by IFN receptor blocking antibody or JAK inhibitor treatment. When SAMD9 expression was knocked down by RNA interference, apoptotic cell death induced by HVJ-E was blocked in U251MG cells. Suppression of SAMD9 using SAMD9 siRNA also inhibited IFN-beta-induced death in U251MG cells with a small, but significant, difference to control groups. However, overexpression of the SAMD9 gene failed to induce significant cell death in U251MG cells. Thus, SAMD9 could be a key molecule to control cancer cell death by HVJ-E or IFN-beta treatment.

PMID:
19830690
DOI:
10.1002/ijc.24965
[Indexed for MEDLINE]
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