Malignant glioma: genetics and biology of a grave matter

Maher, Elizabeth A.; Furnari, Frank B.; Bachoo, Robert; Rowitch, David H.; Louis, David N.; Cavenee, Webster K.; DePinho, Ronald A.

doi:10.1101/gad.891601

Cited by 1,103 publications

(950 citation statements)

References 170 publications

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“…EGFR activation promotes cell growth of astrocyte precursors and neural stem cells (Reynolds et al, 1992;Seidman et al, 1997;Kornblum et al, 1998). In high-grade astrocytomas, the most common type of glioma, approximately 50% of cases exhibit EGFR amplification, and this activation appears critical in the transformation process (Maher et al, 2001;Wechsler-Reya and Scott, 2001). However, in animal models, only EGFR mutation is not sufficient for tumor generation.…”

Section: Growth Factors As Glioma Treatment Targetsmentioning

confidence: 99%

Neuronal stem cells in the central nervous system and in human diseases

Wang

2012

Protein Cell

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The process of cortical expansion in the central nervous system is a key step of mammalian brain development to ensure its physiological function. Radial glial (RG) cells are a glial cell type contributing to this progress as intermediate neural progenitor cells responsible for an increase in the number of cortical neurons. In this review, we discuss the current understanding of RG cells during neurogenesis and provide further information on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis. Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these diseases.

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Section: Growth Factors As Glioma Treatment Targetsmentioning

confidence: 99%

Neuronal stem cells in the central nervous system and in human diseases

Wang

2012

Protein Cell

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“…Malignant astrocytic tumors occur in the human population at a frequency of 7 per 100 000 per year (Rasheed et al, 1999;Maher et al, 2001), making them the most common form of primary brain tumor. There is currently no effective curative therapy for patients with WHO classification Grade IV glioblastomas (also designated as glioblastoma multiforme (GBM)) and the average survival time from diagnosis is approximately 9-11 months (Kleihues et al, 1993;McLendon et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5

et al. 2005

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Glioblastoma multifome is the most common and most aggressive primary brain tumor with no current curative therapy. We found expression of the bZip transcription factor ATF5 in all 29 human glioblastomas and eight human and rat glioma cell lines assessed. ATF5 is not detectably expressed by mature brain neurons and astrocytes, but is expressed by reactive astrocytes. Interference with ATF5 function or expression in all glioma cell lines tested causes marked apoptotic cell death. In contrast, such manipulations do not affect survival of ATF5-expressing cultured astrocytes or of several other cell types that express this protein. In a proof-of-principle experiment, retroviral delivery of a function-blocking mutant form of ATF5 into a rat glioma model evokes death of the infected tumor cells, but not of infected brain cells outside the tumors. The widespread expression of ATF5 in glioblastomas and the selective effect of interference with ATF5 function/expression on their survival suggest that ATF5 may be an attractive target for therapeutic intervention in such tumors.

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“…They are highly invasive and considered to be among the deadliest of human cancers. 1 A hallmark of glioma progression is that transition from lower-grade tumors to GBMs is accompanied by a striking induction of angiogenesis. 1 Therefore, inhibition of angiogenesis may represent a potentially promising strategy in the treatment of gliomas.…”

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confidence: 99%

Interleukin‐6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1

Loeffler

Fayard

Weis

et al. 2005

Intl Journal of Cancer

188

134

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Interleukin-6 (IL-6) expression is strongly correlated with the degree of human glioma malignancy and necessary for tumor formation in a mouse model of spontaneous astrocytomas. Yet, exactly how IL-6 contributes to malignant progression of these brain tumors is still unclear. We have scrutinized the mechanism of transcriptional activation of vascular endothelial growth factor (VEGF) expression by IL-6 in the mouse brain and in glioblastoma cells. We demonstrate here that IL-6 drives transcriptional upregulation of VEGF in astrocytes in vivo using glial fibrillary acidic protein (GFAP)-IL-6/VEGF-green fluorescent protein (GFP) double transgenic mice. We further show that IL-6-induced VEGF transcription and VEGF secretion by human glioblastoma cells is dependent on signal transducer and activator of transcription 3 (STAT3). By progressive 5 0 -deletion analysis we defined the minimal VEGF promoter region for IL-6-responsiveness to nucleotides 288/250. Surprisingly, this promoter region is rich in GC-boxes and does not contain STAT3 binding elements. Electrophoretic mobility shift and supershift assays revealed binding of Sp1 and Sp3 to the 288/250 element upon IL-6 stimulation. Interestingly, preincubation with STAT3 antibody prevented the binding of Sp1 and Sp3 to the 288/250 element, indicating that STAT3 is involved in IL-6-driven Sp1/Sp3 protein-DNA complex formation. Physical interaction of STAT3 and Sp1 was demonstrated by coimmunoprecipitation. The functional relevance of the STAT3/ Sp1 association was corroborated by transient transfection experiments, which showed that overexpression of constitutively active STAT3 increased the minimal VEGF promoter activity. Taken together, our study suggests that IL-6 promotes tumor angiogenesis in gliomas and describes a novel transcriptional activation mechanism for STAT3 in the context of a STAT3 binding element (SBE)-free promoter. ' 2005 Wiley-Liss, Inc.

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Malignant glioma: genetics and biology of a grave matter

Cited by 1,103 publications

References 170 publications

Neuronal stem cells in the central nervous system and in human diseases

Neuronal stem cells in the central nervous system and in human diseases

Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5

Interleukin‐6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1

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