NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.

Members of the nuclear factor of activated T cells (NFAT) family have been identified as regulators of oncogenic transformation in several human malignancies. A prominent member of this family, NFAT1, is associated with tumor cell survival, apoptosis, migration and invasion. Here, we investigated th...

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Main Authors: Xinxin Tie, Sheng Han, Lingxuan Meng, Yunjie Wang, Anhua Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3675208?pdf=render
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spelling doaj-ccfa55262f10449583c54e8dd13e042d2020-11-25T01:57:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6600810.1371/journal.pone.0066008NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.Xinxin TieSheng HanLingxuan MengYunjie WangAnhua WuMembers of the nuclear factor of activated T cells (NFAT) family have been identified as regulators of oncogenic transformation in several human malignancies. A prominent member of this family, NFAT1, is associated with tumor cell survival, apoptosis, migration and invasion. Here, we investigated the role of NFAT1 in glioma cells. In 111 clinical samples, microarray analysis demonstrated that NFAT1 was over-expressed in glioblastoma multiforme (GBM), compared with low-grade gliomas, a result confirmed by RT-PCR in 24 clinical samples and in the U87 and U251 cell lines. Immunohistochemistry and immunofluorescence stain indicated that over-expressed NFAT1 was mainly located in the nucleus, where it acted as a transcription factor. After treatment with the NFAT antagonist cyclosporin A (CsA) and FK506, levels of NFAT1 in the nuclei of U87 GBM cells were dramatically reduced. The invasive potential of U87 cells was reduced by the same treatment, as well as by inhibition of NFAT1 expression using small hairpin RNA. Proliferation of U87 cells was unaffected by CsA, FK506 and NFAT1 shRNA transfection. Clustering analysis and Pearson correlation analysis of microarray data showed that the expression of NFAT1 correlated with the expression of the invasion-related genes cyclooxygenase-2 (COX-2), matrix metalloproteinase-7 (MMP-7) and MMP-9, a result confirmed by in vitro analysis. These findings demonstrate that NFAT1 contributes to the invasive potential but not the proliferation of GBM cells, and suggest that CsA may find application as an adjuvant in combined treatment strategies for GBM.http://europepmc.org/articles/PMC3675208?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Xinxin Tie
Sheng Han
Lingxuan Meng
Yunjie Wang
Anhua Wu
spellingShingle Xinxin Tie
Sheng Han
Lingxuan Meng
Yunjie Wang
Anhua Wu
NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
PLoS ONE
author_facet Xinxin Tie
Sheng Han
Lingxuan Meng
Yunjie Wang
Anhua Wu
author_sort Xinxin Tie
title NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
title_short NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
title_full NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
title_fullStr NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
title_full_unstemmed NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
title_sort nfat1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description Members of the nuclear factor of activated T cells (NFAT) family have been identified as regulators of oncogenic transformation in several human malignancies. A prominent member of this family, NFAT1, is associated with tumor cell survival, apoptosis, migration and invasion. Here, we investigated the role of NFAT1 in glioma cells. In 111 clinical samples, microarray analysis demonstrated that NFAT1 was over-expressed in glioblastoma multiforme (GBM), compared with low-grade gliomas, a result confirmed by RT-PCR in 24 clinical samples and in the U87 and U251 cell lines. Immunohistochemistry and immunofluorescence stain indicated that over-expressed NFAT1 was mainly located in the nucleus, where it acted as a transcription factor. After treatment with the NFAT antagonist cyclosporin A (CsA) and FK506, levels of NFAT1 in the nuclei of U87 GBM cells were dramatically reduced. The invasive potential of U87 cells was reduced by the same treatment, as well as by inhibition of NFAT1 expression using small hairpin RNA. Proliferation of U87 cells was unaffected by CsA, FK506 and NFAT1 shRNA transfection. Clustering analysis and Pearson correlation analysis of microarray data showed that the expression of NFAT1 correlated with the expression of the invasion-related genes cyclooxygenase-2 (COX-2), matrix metalloproteinase-7 (MMP-7) and MMP-9, a result confirmed by in vitro analysis. These findings demonstrate that NFAT1 contributes to the invasive potential but not the proliferation of GBM cells, and suggest that CsA may find application as an adjuvant in combined treatment strategies for GBM.
url http://europepmc.org/articles/PMC3675208?pdf=render
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