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Cell Tissue Res. 2015 Jan;359(1):225-54. doi: 10.1007/s00441-014-2046-y. Epub 2014 Nov 23.

Deregulated proliferation and differentiation in brain tumors.

Author information

1
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, SE-751 85, Sweden.

Abstract

Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment resistance, suppress tumor growth, and prevent recurrence in patients.

PMID:
25416506
PMCID:
PMC4286433
DOI:
10.1007/s00441-014-2046-y
[Indexed for MEDLINE]
Free PMC Article

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