RRC ID 38179
Author Tanaka M, Shimbo T, Kikuchi Y, Matsuda M, Kaneda Y.
Title 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.
Journal Int. J. Cancer
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.
Volume 126(8)
Pages 1982-1991
Published 2010-4-15
DOI 10.1002/ijc.24965
PMID 19830690
MeSH Animals Antineoplastic Agents / pharmacology* Apoptosis / physiology Blotting, Western Cell Line, Tumor Cell Separation Enzyme-Linked Immunosorbent Assay Flow Cytometry Glioma / genetics* Glioma / therapy* Humans Interferon Type I / metabolism Interferon Type I / pharmacology* Male Mice Mice, SCID Oligonucleotide Array Sequence Analysis Oncolytic Virotherapy / methods* Proteins / genetics* Proteins / metabolism RNA Interference Recombinant Proteins / metabolism Recombinant Proteins / pharmacology Reverse Transcriptase Polymerase Chain Reaction Sendai virus / immunology Virion / immunology Virus Inactivation Xenograft Model Antitumor Assays
IF 4.982
Times Cited 30
Human and Animal Cells