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Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

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...

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Autores principales: Huang, Yin-Cheng, Wei, Kuo-Chen, Chang, Chen-Nen, Chen, Pin-Yuan, Hsu, Peng-Wei, Chen, Carl P., Lu, Chin-Song, Wang, Hung-Li, Gutmann, David H., Yeh, Tu-Hsueh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172767/
https://www.ncbi.nlm.nih.gov/pubmed/25247996
http://dx.doi.org/10.1371/journal.pone.0108228
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author Huang, Yin-Cheng
Wei, Kuo-Chen
Chang, Chen-Nen
Chen, Pin-Yuan
Hsu, Peng-Wei
Chen, Carl P.
Lu, Chin-Song
Wang, Hung-Li
Gutmann, David H.
Yeh, Tu-Hsueh
author_facet Huang, Yin-Cheng
Wei, Kuo-Chen
Chang, Chen-Nen
Chen, Pin-Yuan
Hsu, Peng-Wei
Chen, Carl P.
Lu, Chin-Song
Wang, Hung-Li
Gutmann, David H.
Yeh, Tu-Hsueh
author_sort Huang, Yin-Cheng
collection PubMed
description 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.
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spelling pubmed-41727672014-10-02 Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma Huang, Yin-Cheng Wei, Kuo-Chen Chang, Chen-Nen Chen, Pin-Yuan Hsu, Peng-Wei Chen, Carl P. Lu, Chin-Song Wang, Hung-Li Gutmann, David H. Yeh, Tu-Hsueh PLoS One Research Article 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. Public Library of Science 2014-09-23 /pmc/articles/PMC4172767/ /pubmed/25247996 http://dx.doi.org/10.1371/journal.pone.0108228 Text en © 2014 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Huang, Yin-Cheng
Wei, Kuo-Chen
Chang, Chen-Nen
Chen, Pin-Yuan
Hsu, Peng-Wei
Chen, Carl P.
Lu, Chin-Song
Wang, Hung-Li
Gutmann, David H.
Yeh, Tu-Hsueh
Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma
title Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma
title_full Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma
title_fullStr Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma
title_full_unstemmed Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma
title_short Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma
title_sort transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172767/
https://www.ncbi.nlm.nih.gov/pubmed/25247996
http://dx.doi.org/10.1371/journal.pone.0108228
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