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A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Breast cancer expresses functional NMDA receptors
William G North1, Guohong Gao, Vincent A Memoli
1Dartmouth Medical School, Lebanon, NH 03756, USA, william.g.north@dartmouth.edu
Breast Cancer Research and Treatment
|September 29, 2009
Summary
Functional N-methyl-D-aspartate receptors (NMDARs) are present in breast cancer cells and tumors. Blocking these receptors significantly inhibits breast cancer growth and tumor xenografts in mice, indicating their importance for cancer survival.
Area of Science:
- Oncology
- Neuroscience
- Molecular Biology
Background:
- N-methyl-D-aspartate receptors (NMDARs) are critical in the central nervous system.
- Their role in cancer, particularly breast cancer, is largely unexplored.
Purpose of the Study:
- To investigate the expression and function of NMDAR1 and NMDAR2 receptors in breast cancer cells and tumors.
- To determine the impact of NMDAR antagonists on breast cancer growth.
Main Methods:
- RT-PCR to detect NMDAR1 and NMDAR2 mRNA in breast cancer cell lines (Mcf-7, SKBR3).
- Western blotting to confirm protein expression.
- In vitro cell growth assays using NMDAR antagonists (MK-801, memantine).
- Immunohistochemistry on human breast tumor tissues.
- In vivo tumor xenograft studies in mice.
Main Results:
- NMDAR1 and NMDAR2 mRNA and proteins are expressed in Mcf-7 and SKBR3 breast cancer cell lines.
- NMDAR antagonists MK-801 and memantine significantly inhibited cell growth (P < 0.0001).
- Immunohistochemistry confirmed NMDAR1 expression in all examined high-grade breast tumors.
- MK-801 completely arrested tumor xenograft growth in mice.
Conclusions:
- Active NMDAR receptors are expressed in most breast cancers.
- NMDARs play a crucial role in breast cancer cell survival and tumor growth.
- Targeting NMDARs represents a potential therapeutic strategy for breast cancer.
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