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FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration.

ABSTRACT: The transcription factor FOXP3 plays an essential role in regulatory T cell development and function. In addition, it has recently been identified as a tumor suppressor in different cancers. Here, we report that FOXP3 is expressed in normal brain but strongly down-regulated in glioblastoma (GB) and in corresponding GB stem-like cells growing in culture as neurospheres (GB-NS), as evaluated by real time-PCR and confirmed by immunohistochemistry on an independent set of GB. FOXP3 expression was higher in low-grade gliomas than in GB. Interestingly, we also found that neurosphere generation, a feature present in 58% of the GB that we examined, correlated with lower expression of FOXP3 and shorter patient survival. FOXP3 silencing in one GB-NS expressing measurable levels of the gene caused a significant increase in proliferation and migration as well as highly aggressive growth in xenografts. Conversely, FOXP3 over-expression impaired GB-NS migration and proliferation in vitro. We also demonstrated using ChiP that FOXP3 is a transcriptional regulator of p21 and c-MYC supporting the idea that dysregulated expression of these factors is a major mechanism of tumorigenesis driven by the loss of FOXP3 expression in gliomas. These findings support the assertion that FOXP3 exhibits tumor suppressor activity in glioblastomas.

SUBMITTER: Frattini V

PROVIDER: S-EPMC3717952 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration.

Frattini Véronique V Pisati Federica F Speranza Maria Carmela MC Poliani Pietro Luigi PL Frigé Gianmaria G Cantini Gabriele G Kapetis Dimos D Cominelli Manuela M Rossi Alessandra A Finocchiaro Gaetano G Pellegatta Serena S

Oncotarget 20120922 10

The transcription factor FOXP3 plays an essential role in regulatory T cell development and function. In addition, it has recently been identified as a tumor suppressor in different cancers. Here, we report that FOXP3 is expressed in normal brain but strongly down-regulated in glioblastoma (GB) and in corresponding GB stem-like cells growing in culture as neurospheres (GB-NS), as evaluated by real time-PCR and confirmed by immunohistochemistry on an independent set of GB. FOXP3 expression was hi ...[more]

PMID: 23888189

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Dataset Information

FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration.

Publications

FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration.

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