(Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway

( 最大 2000 件 )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27888
タイトル
(Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway
ファイル
内容記述

Abstract

OBJECTIVE The (pro)renin receptor (PRR) plays an essential role in the early development of the central nervous system by activating the Wnt/β-catenin signaling pathway. The authors investigated the potential role of the PRR in the pathogenesis of glioma. METHODS The authors performed immunohistochemical analysis to detect both the PRR and isocitrate dehydrogenase 1 with mutations involving arginine 132 ( IDH1R132H) in paraffin sections of 31 gliomas. Expression of the PRR and Wnt pathway components in cultured human glioma cell lines (U251MG, U87MG, and T98G) was measured using Western blotting. The effects of PRR short interfering RNA (siRNA) on glioma cell proliferation (WST-1 assay and direct cell counting) and apoptosis (flow cytometry and the caspase-3 assay) were also examined. RESULTS PRR expression was significantly higher in glioblastoma than in normal tissue or in lower grade glioma, regardless of IDH1R132H mutation. PRR expression was also higher in human glioblastoma cell lines than in human astrocytes. PRR expression showed a significant positive correlation with the Ki-67 labeling index, while it had a significant negative correlation with the survival time of glioma patients. Treatment with PRR siRNA significantly reduced expression of Wnt2, activated β-catenin, and cyclin D1 by human glioblastoma cell lines, and it reduced the proliferative capacity of these cell lines and induced apoptosis. CONCLUSIONS This is the first evidence that the PRR has an important role in development of glioma by aberrant activation of the Wnt/β-catenin signaling pathway. This receptor may be both a prognostic marker and a therapeutic target for glioma.

KEYWORDS:

(pro)renin receptor; DAB = 3,3′-diaminobenzidine; FITC = fluorescein isothiocyanate; GBM = glioblastoma; GSC = glioma stem cell; IDH1 = isocitrate dehydrogenase 1; IHC = immunohistochemical; IgG = immunoglobulin G; PBS = phosphate-buffered saline; PI = propidium iodide; PRR = (pro)renin receptor; V-ATPase = vacuolar H+-adenosine triphosphatase; Wnt/β-catenin signaling pathway; glioma; oncology; siRNA = short interfering RNA

(医博甲667)

著者
著者 河内 雅章
著者(ヨミ) コウチ マサアキ
著者(別表記) Kouchi Masaaki
掲載誌
Journal of Neurosurgery
掲載誌(別表記)
J Neurosurg.
127
4
開始ページ
819
終了ページ
828
出版者
American Association of Neurological Surgeons
出版年月日
2017-01-06
ISSN
0022-3085
NCID
AA11887556
PMID
28059652
DOI
10.3171/2016.9.JNS16431
資料タイプ
学位論文
言語
英語
関連情報URL
https://doi.org/10.3171/2016.9.JNS16431
関連情報(isVersionOf)
Publisher's Version.
該当なし
学位授与番号
博甲第667号
学位授与年月日
2017-03-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
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