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.

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.

• Authors: Masahiko Tanaka, Takashi Shimbo, Yasushi Kikuchi, Masahide Matsuda, Yasufumi Kaneda
• Journal: International journal of cancer (Int J Cancer) Vol. 126 Issue 8 Pg. 1982-1991 (Apr 15 2010) ISSN: 1097-0215 [Electronic] United States
• PMID: 19830690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interferon Type I
• Intracellular Signaling Peptides and Proteins
• Proteins
• Recombinant Proteins
• SAMD9 protein, human

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (physiology)
• Blotting, Western
• Cell Line, Tumor
• Cell Separation
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Glioma (genetics, therapy)
• Humans
• Interferon Type I (metabolism, pharmacology)
• Intracellular Signaling Peptides and Proteins
• Male
• Mice
• Mice, SCID
• Oligonucleotide Array Sequence Analysis
• Oncolytic Virotherapy (methods)
• Proteins (genetics, metabolism)
• RNA Interference
• Recombinant Proteins (metabolism, pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sendai virus (immunology)
• Virion (immunology)
• Virus Inactivation
• Xenograft Model Antitumor Assays