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

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27888
Title
(Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway
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Description

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)

Author
著者 河内 雅章
著者(ヨミ) コウチ マサアキ
著者(別表記) Kouchi Masaaki
Publication Title
Journal of Neurosurgery
Publication Title Alternative
J Neurosurg.
Volume
127
Issue
4
Start Page
819
End Page
828
Publisher
American Association of Neurological Surgeons
Published Date
2017-01-06
ISSN
0022-3085
NCID
AA11887556
PMID
28059652
DOI
10.3171/2016.9.JNS16431
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.3171/2016.9.JNS16431
Relation(isVersionOf)
Publisher's Version.
Text Version
none
Grant ID
博甲第667号
Grant Date
2017-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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