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.

journal_name

Int J Cancer

authors

Tanaka M,Shimbo T,Kikuchi Y,Matsuda M,Kaneda Y

doi

10.1002/ijc.24965

subject

Has Abstract

pub_date

2010-04-15 00:00:00

pages

1982-1991

issue

8

eissn

0020-7136

issn

1097-0215

journal_volume

126

pub_type

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