title: Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma.
abstract: Most meningiomas are benign, but some clinical-aggressive tumors exhibit brain invasion and cannot be resected without significant complications. To identify molecular markers for these clinically-aggressive meningiomas, we performed microarray analyses on 24 primary cultures from 21 meningiomas and 3 arachnoid membranes. Using this approach, increased transglutaminase 2 (TGM2) expression was observed, which was subsequently validated in an independent set of 82 meningiomas by immunohistochemistry. Importantly, the TGM2 expression level was associated with increasing WHO malignancy grade as well as meningioma recurrence. Inhibition of TGM2 function by siRNA or cystamine induced meningioma cell death, which was associated with reduced AKT phosphorylation and caspase-3 activation. Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth.
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Yin-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Chen-Nen
authors.initials: CN
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Peng-Wei
authors.initials: PW
authors.lastname: Hsu
authors.affiliation: Department of Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Carl P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Chin-Song
authors.initials: CS
authors.lastname: Lu
authors.affiliation: Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Hung-Li
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Neurology, Washington University, School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Tu-Hsueh
authors.initials: TH
authors.lastname: Yeh
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008577:Meningeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D008579:Meningioma / Q000201:enzymology* / Q000473:pathology; D060787:Neoplasm Grading; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D019204:GTP-Binding Proteins