Enhanced expression of NADPH oxidase Nox4 in human gliomas and its roles in cell proliferation and survival.
Reactive oxygen species (ROS) have been attracting attention as mediators of various cell-signaling pathways. Nox-family NADPH oxidases have proven to be a major source of ROS production in various cell types and have crucial roles in various physiological and pathological processes. In this study, we show that Nox4, a member of Nox family, is prominently expressed in various neuroepithelial tumors by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical studies. We quantified Nox4 mRNA expression by real-time PCR in tumor specimens from 58 patients with astrocytomas and found that the expression levels of Nox4 mRNA in glioblastomas (WHO grade IV) were significantly higher than those in other astrocytomas (WHO grade II and III). In addition, we show that specific knockdown of Nox4 expression by RNA interference results in cell-growth inhibition and enhances induction of apoptosis by chemotherapeutic agents, such as cisplatin, in cultured glioma cell lines. Based on these observations, enhanced expression of Nox4 appears to be involved in cell proliferation and survival in glioma cells.
Shono
Tadahisa
T
Department of Neurosurgery, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan. tshono@ns.med.kyushu-u.ac.jp
Yokoyama
Nobuhiko
N
Uesaka
Toshio
T
Kuroda
Junya
J
Takeya
Ryu
R
Yamasaki
Tomoko
T
Amano
Toshiyuki
T
Mizoguchi
Masahiro
M
Suzuki
Satoshi O
SO
Niiro
Hiroaki
H
Miyamoto
Kyoko
K
Akashi
Koichi
K
Iwaki
Toru
T
Sumimoto
Hideki
H
Sasaki
Tomio
T
D017209:Apoptosis / Q000502:physiology; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D012333:RNA, Messenger; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human