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Silencing of selected glutamate receptor subunits modulates cancer growth

Hella Luksch1, Ortrud Uckermann, Andrzej Stepulak

  • 1Department of Pediatric Neurology, Children's Hospital, University of Technology, Dresden, Germany.

Anticancer Research
|October 4, 2011
PubMed
Abstract

Insights

Silencing glutamate receptor subunits impacts cancer. Reduced GLUR4 expression boosts cancer cell proliferation, while reduced NR1 expression inhibits it, affecting malignant phenotype pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Neuroscience

Background:

  • Emerging evidence suggests glutamate plays a role in cancer biology.
  • This study investigates the impact of glutamate receptor subunit silencing on cancer cell phenotype.

Purpose of the Study:

  • To determine the effect of silencing specific glutamate receptor subunits (GLUR4, NR1, KA2, NR2D) on cancer cell proliferation and migration.
  • To analyze the modulation of cancer-related gene expression following glutamate receptor subunit silencing.

Main Methods:

  • Stable transfection of human cancer cell lines (TE671, RPMI8226, A549) with fragments of GLUR4, NR1, KA2, and NR2D.
  • Assay of cell proliferation, migration, and mRNA expression using the Human Cancer PathwayFinder™ PCR Array.

Main Results:

  • Decreased GLUR4 expression significantly increased cancer cell proliferation.
  • Decreased NR1 expression significantly reduced cancer cell proliferation.
  • Knockdown of KA2 and NR2D did not affect cancer phenotype.
  • GLUR4 gene silencing modulated mRNA expression of genes involved in invasion, metastasis, tumor suppression, oncogenesis, and cell adhesion.

Conclusions:

  • Glutamate receptor subunits expressed on cancer cells are implicated in biochemical pathways regulating malignant phenotype.
  • Specific subunits, GLUR4 and NR1, play opposing roles in regulating cancer cell proliferation.

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