RRC ID |
52241
|
著者 |
Kikuchi R, Sampetrean O, Saya H, Yoshida K, Toda M.
|
タイトル |
Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells.
|
ジャーナル |
J Neurooncol
|
Abstract |
DEP domain containing 1 (DEPDC1) is a novel oncoantigen expressed in cancer cells, which presents oncogenic activity and high immunogenicity. Although DEPDC1 has been predicted to be a useful antigen for the development of a cancer vaccine, its pathophysiological roles in glioma have not been investigated. Here, we analyzed the expression and function of DEPDC1 in malignant glioma. DEPDC1 expression in glioma cell lines, glioma tissues, and brain tumor initiating cells (BTICs) was assessed by western blot and quantitative polymerase chain reaction (PCR). The effect of DEPDC1 downregulation on cell growth and nuclear factor kappa B (NFκB) signaling in glioma cells was investigated. Overall survival was assessed in mouse glioma models using human glioma cells and induced mouse brain tumor stem cells (imBTSCs) to determine the effect of DEPDC1 suppression in vivo. DEPDC1 expression was increased in glioma cell lines, tissues, and BTICs. Suppression of endogenous DEPDC1 expression by small interfering RNA (siRNA) inhibited glioma cell viability and induced apoptosis through NFκB signaling. In mouse glioma models using human glioma cells and imBTSCs, downregulation of DEPDC1 expression prolonged overall survival. These results suggest that DEPDC1 represents a target molecule for the treatment of glioma.
|
巻・号 |
133(2)
|
ページ |
297-307
|
公開日 |
2017-6-1
|
DOI |
10.1007/s11060-017-2457-1
|
PII |
10.1007/s11060-017-2457-1
|
PMID |
28555424
|
MeSH |
Animals
Brain Neoplasms / genetics
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Proliferation / genetics
Cell Survival / physiology
Female
GTPase-Activating Proteins / genetics
GTPase-Activating Proteins / metabolism*
Gene Expression Regulation, Neoplastic / genetics*
Glioma / metabolism*
Glioma / pathology
Humans
Male
Mice
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
RNA, Messenger / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Repressor Proteins / metabolism
Time Factors
|
IF |
3.06
|
引用数 |
6
|
リソース情報 |
ヒト・動物細胞 |
U251(RCB0461) |