Research article summary (published 30 May 2008):

Knockdown of GluR1 expression by RNA interference inhibits glioma proliferation.

Full 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.

Author information

Author/s: de Groot, John F (JF); Piao, Yuji (Y); Lu, Li (L); Fuller, Gregory N (GN); Yung, W K Alfred (WK);

Affiliation: Brain Tumor Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. jdegroot(-atsign-)mdanderson.org

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neuro-oncology (J Neurooncol), published in Netherlands. (Language: eng)

Reference: 2008-Jun; vol 88 (issue 2) : pp 121-33

Dates: Created 2008/09/05; Completed 2008/11/05;

PMID: 18317690, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Brain Neoplasms - metabolism; pathology; prevention & control Carcinogenicity Tests Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Down-Regulation - drug effects; genetics Gene Expression Regulation - drug effects; genetics Glioma - metabolism; pathology; prevention & control Humans

Humans Ki-67 Antigen - metabolism Mice Mice, Nude Microarray Analysis - methods RNA Interference - physiology RNA, Double-Stranded - pharmacology RNA, Small Interfering - pharmacology; therapeutic use Receptors, AMPA - genetics; metabolism Signal Transduction - drug effects

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Ki-67 Antigen (0) ; RNA, Double-Stranded (0) ; RNA, Small Interfering (0) ; Receptors, AMPA (0) ; glutamate receptor ionotropic, AMPA 1 (0)

Related articles

These are the most related articles currently in our database:

• Intraperitoneal injection of a hairpin RNA-expressing plasmid targeting urokinase-type plasminogen activator (uPA) receptor and uPA retards angiogenesis and inhibits intracranial tumor growth in nude mice. 13 Jul 2007
• Downregulation of laminin alpha4 chain expression inhibits glioma invasion in vitro and in vivo. 18 Oct 2005
• Dietary prevention of malignant glioma aggressiveness, implications in oxidant stress and apoptosis. 13 Jul 2008
• Identification of potential genes regulated by DNA methyltransferase 3B in a hepatocellular carcinoma cell line by RNA interference and microarray analysis. 30 Oct 2005
• Therapeutic vaccination against malignant gliomas based on allorecognition and syngeneic tumor antigens: proof of principle in two strains of rat. 11 Feb 2008
• Antagonism of transforming growth factor-Beta signaling inhibits fibrosis-related genes. 29 Sep 2005
• Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. 13 Feb 2006
• Serum-dependence of AMPA receptor-mediated proliferation in glioma cells. 29 Apr 2006
• RNA interference targeting the R2 subunit of ribonucleotide reductase inhibits growth of tumor cells in vitro and in vivo. 30 Mar 2007
• Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of experimental intracranial human malignant glioma. 30 May 1999

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a larger map of 100+ related articles.