Knockdown of GluR1 expression by RNA interference inhibits glioma proliferation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-06

AUTHORS

John F. de Groot, Yuji Piao, Li Lu, Gregory N. Fuller, W. K. Alfred Yung

ABSTRACT

High-grade gliomas release excitotoxic concentrations of glutamate which contributes to their malignant phenotype. To improve our understanding of the mechanisms by which glutamate enhances tumor growth and invasion, we examined alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated signaling in glioma cell lines. shRNA was used to stably knockdown GluR1, the most abundant AMPA receptor subunit in glioma, to evaluate its role in tumor signaling, proliferation and tumorigenicity. In a tissue array, there was a statistically significant increase in GluR1 expression in glioblastoma samples compared to anaplastic astrocytoma and low-grade tumors. In vitro, we observed a time and dose-dependent increase in MAPK phosphorylation following exposure to AMPA, which was blocked with AMPA receptor antagonists and the MEK1 inhibitor PD98059. Retroviral delivery of GluR1 shRNA in U251 and U87 glioma cells reduced GluR1 protein expression, inhibited AMPA-mediated increases in MAPK phosphorylation, and decreased glioma proliferation in vitro. U251 and U87 shGluR1 cells implanted into the flanks of nude mice grew slower than controls, which correlated with a decrease in proliferation measured by Ki-67 staining and an increase in apoptosis. These results suggest that AMPA receptors are abundantly expressed in high-grade gliomas and gene silencing of the GluR1 AMPA receptor subunit results in abrogation of AMPA-mediated signaling and tumor growth. More... »

PAGES

121-133

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11060-008-9552-2

DOI

http://dx.doi.org/10.1007/s11060-008-9552-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032937995

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18317690


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s11060-008-9552-2'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s11060-008-9552-2'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s11060-008-9552-2'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s11060-008-9552-2'


 

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